Fine control of drug delivery for cochlear implant applications

Cochlear implants are neuroprostheses that are inserted into the inner ear to directly electrically stimulate the auditory nerve, thus replacing lost cochlear receptors, the hair cells. The reduction of the gap between electrodes and nerve cells will contribute to technological solutions simultaneously increasing the frequency resolution, the sound quality and the amplification of the signal. Recent findings indicate that neurotrophins (NTs) such as brain derived neurotrophic factor (BDNF) stimulate the neurite outgrowth of auditory nerve cells by activating Trk receptors on the cellular surface (1–3). Furthermore, small-size TrkB receptor agonists such as di-hydroxyflavone (DHF) are now available, which activate the TrkB receptor with similar efficiency as BDNF, but are much more stable (4). Experimentally, such molecules are currently used to attract nerve cells towards, for example, the electrodes of cochlear implants. This paper analyses the scenarios of low dose aspects of controlled release of small-size Trk receptor agonists from the coated CI electrode array into the inner ear. The control must first ensure a sufficient dose for the onset of neurite growth. Secondly, a gradient in concentration needs to be maintained to allow directive growth of neurites through the perilymph-filled gap towards the electrodes of the implant. We used fluorescein as a test molecule for its molecular size similarity to DHF and investigated two different transport mechanisms of drug dispensing, which both have the potential to fulfil controlled low-throughput drug-deliverable requirements. The first is based on the release of aqueous fluorescein into water through well-defined 60-μm size holes arrays in a membrane by pure osmosis. The release was both simulated using the software COMSOL and observed experimentally. In the second approach, solid fluorescein crystals were encapsulated in a thin layer of parylene (PPX), hence creating random nanometer-sized pinholes. In this approach, the release occurred due to subsequent water diffusion through the pinholes, dissolution of the fluorescein and then release by out-diffusion. Surprisingly, the release rate of solid fluorescein through the nanoscopic scale holes was found to be in the same order of magnitude as for liquid fluorescein release through microscopic holes.

Use of Echogenic Immunoliposomes for Delivery of both Drug and Stem Cells for Inhibition of Atheroma Progression

Use of Echogenic Immunoliposomes for Delivery of both Drug and Stem Cells for Inhibition of Atheroma Progression By Ali K. Naji B.S. Advisor: Dr. Melvin E. Klegerman PhD Background and significance: Echogenic liposomes can be used as drug and cell delivery vehicles that reduce atheroma progression. Vascular endothelial growth factor (VEGF) is a signal protein that induces vasculogenesis and angiogenesis. VEGF functionally induces migration and proliferation of endothelial cells and increases intracellular vascular permeability. VEGF activates angiogenic transduction factors through VEGF tyrosine kinase domains in high-affinity receptors of endothelial cells. Bevacizumab is a humanized monoclonal antibody specific for VEGF-A which was developed as an anti-tumor agent. Often, anti-VEGF agents result in regression of existing microvessels, inhibiting tumor growth and possibly causing tumor shrinkage with time. During atheroma progression neovasculation in the arterial adventitia is mediated by VEGF. Therefore, bevacizumab may be effective in inhibiting atheroma progression. Stem cells show an ability to inhibit atheroma progression. We have previously demonstrated that monocyte derived CD-34+ stem cells that can be delivered to atheroma by bifunctional-ELIP ( BF-ELIP) targeted to Intercellular Adhesion Molecule-1 (ICAM-1) and CD-34. Adhesion molecules such as ICAM-1 and vascular cell adhesion molecule-1 (VCAM-1) are expressed by endothelial cells under inflammatory conditions. Ultrasound enhanced liposomal targeting provides a method for stem cell delivery into atheroma and encapsulated drug release. This project is designed to examine the ability of echogenic liposomes to deliver bevacizumab and stem cells to inhibit atheroma progression and neovasculation with and without ultrasound in vitro and optimize the ultrasound parameters for delivery of bevacizumab and stem cells to atheroma. V Hypotheses: Previous studies showed that endothelial cell VEGF expression may relate to atherosclerosis progression and atheroma formation in the cardiovascular system. Bevacizumab-loaded ELIP will inhibit endothelial cell VEGF expression in vitro. Bevacizumab activity can be enhanced by pulsed Doppler ultrasound treatment of BEV-ELIP. I will also test the hypothesis that the transwell culture system can serve as an in vitro model for study of US-enhanced targeted delivery of stem cells to atheroma. Monocyte preparations will serve as a source of CD34+ stem cells. Specific Aims: Induce VEGF expression using PKA and PKC activation factors to endothelial cell cultures and use western blot and ELISA techniques to detect the expressed VEGF.  Characterize the relationship between endothelial cell proliferation and VEGF expression to develop a specific EC culture based system to demonstrate BEV-ELIP activity as an anti-VEGF agent. Design a cell-based assay for in vitro assessment of ultrasound-enhanced bevacizumab release from echogenic liposomes.  Demonstrate ultrasound delivery enhancement of stem cells by applying different types of liposomes on transwell EC culture using fluorescently labeled monocytes and detect the effect on migration and attachment rate of these echogenic liposomes with and without ultrasound in vitro.

Nd, Sr and Pb isotopic composition of eolian dust deposited in the central North Pacific

The silicate fractions of recent pelagic sediments in the central north Pacific Ocean are dominated by eolian dust derived from central Asia. An 11 Myr sedimentary record at ODP Sites 885/886 at 44.7°N, 168.3°W allows the evaluation of how such dust and its sources have changed in response to late Cenozoic climate and tectonics. The extracted eolian fraction contains variable amounts (>70%) of clay minerals with subordinate quartz and plagioclase. Uniform Nd isotopic compositions (epsilon-Nd =38.6 to 310.5) and Sm/Nd ratios (0.170-0.192) for most of the 11 Myr record demonstrate a well-mixed provenance in the basins north of the Tibetan Plateau and the Gobi Desert that was a source of dust long before the oldest preserved Asian loess formed. epsilon-Nd values of up to 36.5 for samples 62.9 Ma indicate <=35 wt% admixture of a young, Kamchatka-like volcanic arc component. The coherence of Pb and Nd in the erosional cycle allows us to constrain the Pb isotopic composition of Asian loess devoid of anthropogenic contamination to 206Pb/204Pb =18.97 +/- 0.06, 207Pb/204Pb =15.67 +/- 0.02, 208Pb/204Pb =39.19 +/- 0.11. 87Sr/86Sr (0.711-0.721) and Rb/Sr ratios (0.39-1.1) vary with dust mineralogy and provide an age indication of ~250 Ma. 40Ar/39Ar ages of six dust samples are uniform around 200 Ma and match the K-Ar ages of modern dust deposited on Hawaii. These data reflect the weighted age average of illite formation. Changes from illite- smectite with significant kaolinite to illite- and chlorite-rich, kaolinite-free assemblages since the late Pliocene document changes in the intensity of chemical weathering in the source region. Such weathering evidently did not disturb the K-Ar systematics, and only induced scatter in the Rb-Sr data. We propose that when smectite forms at the expense of illite, K and Ar are quantitatively lost from what becomes smectite, but are quantitatively retained in adjacent illite layers. 40Ar/39Ar age data, therefore, are insensitive to smectite formation during chemical weathering but date the diagenetic growth of illite, the major K-bearing phase in the dust. Over the past 12 Myr, the dust flux to the north Pacific increased by more than an order of magnitude, documenting a substantial drying of central Asia. This climatic change, however, did not alter the ultimate source of the dust, and neoformational products of chemical weathering always remained subordinate to assemblages reworked by mechanical erosion in dust deposited in eastern Asia and the Pacific Ocean.

Producción en masa, economía monetaria y vitalidad comercial del Mediterráneo

Se argumenta que la arqueología y la historia monetaria reúnen entre sí el potencial para proyectar una imagen de la economía romana muy diferente a la que sugieren los estereotipos minimalistas. Se discuten las implicancias de esta argumentación para el período tardoantiguo en particular, rechazando el catastrofismo con el que Rostovtzeff concluía su célebre historia del temprano imperio. En el imperio tardío la fortaleza de los intereses privados se mantuvo tan firme como siempre, en una economía caracterizada por la integración de los negocios públicos y privados antes que por un supuesto conflicto o antagonismo entre ambos. El imperio de Oriente conservó estas tendencias en forma pura, con niveles sostenidos de comercio y circulación monetaria hasta las décadas centrales del siglo VII. En este trabajo se argumenta que pensar en términos de ciclos económicos sería para los historiadores más razonable que la patología convencional de la "declinación", "decadencia", etc. Este patrón es notablemente evidente en la historia económica bizantina, marcada por abruptas fluctuaciones entre los siglos V y XII.

Producción en masa, economía monetaria y vitalidad comercial del Mediterráneo

Se argumenta que la arqueología y la historia monetaria reúnen entre sí el potencial para proyectar una imagen de la economía romana muy diferente a la que sugieren los estereotipos minimalistas. Se discuten las implicancias de esta argumentación para el período tardoantiguo en particular, rechazando el catastrofismo con el que Rostovtzeff concluía su célebre historia del temprano imperio. En el imperio tardío la fortaleza de los intereses privados se mantuvo tan firme como siempre, en una economía caracterizada por la integración de los negocios públicos y privados antes que por un supuesto conflicto o antagonismo entre ambos. El imperio de Oriente conservó estas tendencias en forma pura, con niveles sostenidos de comercio y circulación monetaria hasta las décadas centrales del siglo VII. En este trabajo se argumenta que pensar en términos de ciclos económicos sería para los historiadores más razonable que la patología convencional de la "declinación", "decadencia", etc. Este patrón es notablemente evidente en la historia económica bizantina, marcada por abruptas fluctuaciones entre los siglos V y XII.

Producción en masa, economía monetaria y vitalidad comercial del Mediterráneo

Se argumenta que la arqueología y la historia monetaria reúnen entre sí el potencial para proyectar una imagen de la economía romana muy diferente a la que sugieren los estereotipos minimalistas. Se discuten las implicancias de esta argumentación para el período tardoantiguo en particular, rechazando el catastrofismo con el que Rostovtzeff concluía su célebre historia del temprano imperio. En el imperio tardío la fortaleza de los intereses privados se mantuvo tan firme como siempre, en una economía caracterizada por la integración de los negocios públicos y privados antes que por un supuesto conflicto o antagonismo entre ambos. El imperio de Oriente conservó estas tendencias en forma pura, con niveles sostenidos de comercio y circulación monetaria hasta las décadas centrales del siglo VII. En este trabajo se argumenta que pensar en términos de ciclos económicos sería para los historiadores más razonable que la patología convencional de la "declinación", "decadencia", etc. Este patrón es notablemente evidente en la historia económica bizantina, marcada por abruptas fluctuaciones entre los siglos V y XII.

Phototrophic carbon fixation rates measured in water samples from the Porcupine Abyssal Plains during James Cook cruise JC087

Water samples were collected from pre-dawn CTD casts at 5 depths corresponding to 55%, 20%, 7%, 5% and 1% of surface irradiance. 1 litre water samples wrapped with optical filters to replicate light levels. Spiked with 200 µL of 13C labelled sodium bicarbonate. After 24 hourse filtered through ashed 25mm GF/F (Whatman) filters, rinsed with HCl solution (1-2%) and stored at -20oC. On shore encapsulated in tin capsules and analysed for 13C isotopic enrichment. Carbon uptake rates calculated using the equations of Fernandez et al. (2005).

Seawater carbonate chemistry and Littorina obtusata biological processes during experiments, 2009

Our understanding of the effects of ocean acidification on whole organism function is growing, but most current information is for adult stages of development. Here, we show the effects of reduced pH seawater (pH 7.6) on aspects of the development, physiology and behaviour of encapsulated embryos of the marine intertidal gastropod Littorina obtusata. We found reduced viability and increased development times under reduced pH conditions, and the embryos had significantly altered behaviours and physiologies. In acidified seawater, embryos spent more time stationary, had slower rotation rates, spent less time crawling, but increased their movement periodicity compared with those maintained under control conditions. Larval and adult heart rates were significantly lower in acidified seawater, and hatchling snails had an altered shell morphology (lateral length and spiral shell length) compared to control snails. Our findings show that ocean acidification may have multiple, subtle effects during the early development of marine animals that may have implications for their survival beyond those predicted using later life stages.

Ocean acidification impairs vermetid reef recruitment

Vermetids form reefs in sub-tropical and warm-temperate waters that protect coasts from erosion, regulate sediment transport and accumulation, serve as carbon sinks and provide habitat for other species. The gastropods that form these reefs brood encapsulated larvae; they are threatened by rapid environmental changes since their ability to disperse is very limited. We used transplant experiments along a natural CO2 gradient to assess ocean acidification effects on the reef-building gastropod Dendropoma petraeum. We found that although D. petraeum were able to reproduce and brood at elevated levels of CO2, recruitment success was adversely affected. Long-term exposure to acidified conditions predicted for the year 2100 and beyond caused shell dissolution and a significant increase in shell Mg content. Unless CO2 emissions are reduced and conservation measures taken, our results suggest these reefs are in danger of extinction within this century, with significant ecological and socioeconomic ramifications for coastal systems.

An Aspect-Oriented Approach for Supporting Autonomic Reconfiguration of Software Architecture

The increasing complexity of current software systems is encouraging the development of self-managed software architectures, i.e. systems capable of reconfiguring their structure at runtime to fulfil a set of goals. Several approaches have covered different aspects of their development, but some issues remain open, such as the maintainability or the scalability of self-management subsystems. Centralized approaches, like self-adaptive architectures, offer good maintenance properties but do not scale well for large systems. On the contrary, decentralized approaches, like self-organising architectures, offer good scalability but are not maintainable: reconfiguration specifications are spread and often tangled with functional specifications. In order to address these issues, this paper presents an aspect-oriented autonomic reconfiguration approach where: (1) each subsystem is provided with self-management properties so it can evolve itself and the components that it is composed of; (2) self-management concerns are isolated and encapsulated into aspects, thus improving its reuse and maintenance. Povzetek: Predstavljen je pristop s samo-preoblikovanjem programske arhitekture.

Performance of a transmutation advanced device for sustainable energy application

Preliminary studies have been performed to design a device for nuclear waste transmutation and hydrogen generation based on a gas-cooled pebble bed accelerator driven system, TADSEA (Transmutation Advanced Device for Sustainable Energy Application). In previous studies we have addressed the viability of an ADS Transmutation device that uses as fuel wastes from the existing LWR power plants, encapsulated in graphite in the form of pebble beds, cooled by helium which enables high temperatures (in the order of 1200 K), to generate hydrogen from water either by high temperature electrolysis or by thermochemical cycles. For designing this device several configurations were studied, including several reflectors thickness, to achieve the desired parameters, the transmutation of nuclear waste and the production of 100 MW of thermal power. In this paper new studies performed on deep burn in-core fuel management strategy for LWR waste are presented. The fuel cycle on TADSEA device has been analyzed based on both: driven and transmutation fuel that had been proposed by the General Atomic design of a gas turbine-modular helium reactor. The transmutation results of the three fuel management strategies, using driven, transmutation and standard LWR spent fuel were compared, and several parameters describing the neutron performance of TADSEA nuclear core as the fuel and moderator temperature reactivity coefficients and transmutation chain, are also presented

Towards execution time estimation in abstract machine-based languages

Abstract machines provide a certain separation between platformdependent and platform-independent concerns in compilation. Many of the differences between architectures are encapsulated in the speciflc abstract machine implementation and the bytecode is left largely architecture independent. Taking advantage of this fact, we present a framework for estimating upper and lower bounds on the execution times of logic programs running on a bytecode-based abstract machine. Our approach includes a one-time, programindependent proflling stage which calculates constants or functions bounding the execution time of each abstract machine instruction. Then, a compile-time cost estimation phase, using the instruction timing information, infers expressions giving platform-dependent upper and lower bounds on actual execution time as functions of input data sizes for each program. Working at the abstract machine level makes it possible to take into account low-level issues in new architectures and platforms by just reexecuting the calibration stage instead of having to tailor the analysis for each architecture and platform. Applications of such predicted execution times include debugging/veriflcation of time properties, certiflcation of time properties in mobile code, granularity control in parallel/distributed computing, and resource-oriented specialization.

Analysis of concurrent constraint logic programs with a fixed scheduling rule

The analysis of concurrent constraint programs is a challenge due to the inherently concurrent behaviour of its computational model. However, most implementations of the concurrent paradigm can be viewed as a computation with a fixed scheduling rule which suspends some goals so that their execution is postponed until some condition awakens them. For a certain kind of properties, an analysis defined in these terms is correct. Furthermore, it is much more tractable, and in addition can make use of existing analysis technology for the underlying fixed computation rule. We show how this can be done when the starting point is a framework for the analysis of sequential programs. The resulting analysis, which incorporates suspensions, is adequate for concurrent models where concurrency is localized, e.g. the Andorra model. We refine the analysis for this particular case. Another model in which concurrency is preferably encapsulated, and thus suspensions are local to parts of the computation, is that of CIAO. Nonetheless, the analysis scheme can be generalized to models with global concurrency. We also sketch how this could be done, and we show how the resulting analysis framework could be used for analyzing typical properties, such as suspensión freeness.

Assessing the dynamic behavior of wsn motes and rfid semi-passive tags for temperature monitoring.

A notorious advantage of wireless transmission is a significant reduction and simplification in wiring and harness. There are a lot of applications of wireless systems, but in many occasions sensor nodes require a specific housing to protect the electronics from hush environmental conditions. Nowadays the information is scarce and nonspecific on the dynamic behaviour of WSN and RFID. Therefore the purpose of this study is to evaluate the dynamic behaviour of the sensors. A series of trials were designed and performed covering temperature steps between cold room (5 °C), room temperature (23 °C) and heated environment (35 °C). As sensor nodes: three Crossbow motes, a surface mounted Nlaza module (with sensor Sensirion located on the motherboard), an aerial mounted Nlaza where the Sensirion sensor stayed at the end of a cable), and four tags RFID Turbo Tag (T700 model with and without housing), and 702-B (with and without housing). To assess the dynamic behaviour a first order response approach is used and fitted with dedicated optimization tools programmed in Matlab that allow extracting the time response (?) and corresponding determination coefficient (r2) with regard to experimental data. The shorter response time (20.9 s) is found for the uncoated T 700 tag which encapsulated version provides a significantly higher response (107.2 s). The highest ? corresponds to the Crossbow modules (144.4 s), followed by the surface mounted Nlaza module (288.1 s), while the module with aerial mounted sensor gives a response certainly close above to the T700 without coating (42.8 s). As a conclusion, the dynamic response of temperature sensors within wireless and RFID nodes is dramatically influenced by the way they are housed (to protect them from the environment) as well as by the heat released by the node electronics itself; its characterization is basic to allow monitoring of high rate temperature changes and to certify the cold chain. Besides the time to rise and to recover is significantly different being mostly higher for the latter than for the former.

Diseño y test VHDL de un cambiador de formato para ver TV3D en un televisor convencional

La difusión de TV3D actual utiliza formatos como el Side-by-Side o Top-and-Bottom, en los que cada par de imágenes, correspondiente a las vistas de los ojos derecho e izquierdo, se encapsula con la mitad de la resolución espacial en una sola imagen. Estas imágenes se muestran de manera casi simultánea de forma que el ojo humano compone una imagen con profundidad que se asemeja a la visión binocular natural. Desde hace un par de años las principales plataformas de televisión han empezado a crear canales con contenido 3D. La televisión 3D (TV3D) se ha introducido en los hogares gracias a los televisores estereoscópicos. Estos televisores, que son compatibles con los formatos antes mencionados, extraen de cada imagen sus dos vistas, recuperan la resolución original y presentan cada vista alternativamente en la pantalla, generando al mismo tiempo una señal de sincronismo para las gafas activas, creando de esta forma la sensación tridimensional de las imágenes. En este PFC se pretende realizar el diseño VHDL de un cambiador de formato que genere en tiempo real la secuencia de imágenes correspondiente a los ojos derecho e izquierdo, con resolución completa, a partir de una secuencia codificada en formato tipo Top-and-Bottom y el banco de test para su prueba. Este circuito se implementará como un periférico del procesador NIOS II de Altera. El diseño podría utilizarse como parte de un sistema que permita la visualización de las actuales emisiones de televisión 3D en un televisor convencional. La tecnología de referencia que se utilizará serán las FPGAs, más concretamente la tarjeta Cyclone III FPGA Starter Kit (EP3C25 FPGA) de Altera, junto a una tarjeta de ampliación de Microtronix con entrada y salida HDMI para video y audio. Además se pretende crear la documentación necesaria para el desarrollo de futuros trabajos relacionados con la televisión 3D. ABSTRACT Current TV3D broadcasting uses formats as Side-by-Side or Top-and-Bottom, where every single pair of images, corresponding to left and right eyes views, are encapsulated with half spatial resolution in one single image. These images are almost simultaneously displayed so that the human eye forms an image with depth resembling naturally binocular vision. From a couple of years the major TV platforms have begun to create 3D content channels. 3D Television (3DTV) has been introduced in homes through stereoscopic televisions. These televisions, which are compatible with the above formats, each image is extracted from the two views, and recover the original resolution and displays alternately each view in screen, while generating a synchronization signal for active glasses, thereby creating the three-dimensional sensation of the images. The main objective in this PFC is to make the design of an exchanger VHDL format in real time to generate the image sequence corresponding to the right and left eyes, with full resolution from an encoded sequence type format Top-and-Bottom and test bench for testing. This circuit is implemented as a Altera NIOS II processor peripheral.The design could be used as part of a system enabling the display of current television broadcasts 3D on a conventional television. The reference technology that will be use are FPGAs, more specifically Cyclone III FPGA Starter Card Kit (EP3C25 FPGA) Altera, along with an expansion card Microtronix with HDMI input and output video and audio. It also aims to create documentation for the development of future works related to 3D TV.