Targeted cancer diagnosis with radiolabeled endostatin

Nuclear imaging is used for non-invasive detection, staging and therapeutic monitoring of tumors through the use of radiolabeled probes. Generally, these probes are used for applications in which they provide passive, non-specific information about the target. Therefore, there is a significant need for actively-targeted radioactive probes to provide functional information about the site of interest. This study examined endostatin, an endogenous inhibitor of tumor angiogenesis, which has affinity for tumor vasculature. The major objective of this study was to develop radiolabeled analogues of endostatin through novel chemical and radiochemical syntheses, and to determine their usefulness for tumor imaging using in vitro and in vivo models of vascular, mammary and prostate tumor cells. I hypothesize that this binding will allow for a non-invasive approach to detection of tumor angiogenesis, and such detection can be used for therapeutic monitoring to determine the efficacy of anti-angiogenic therapy. ^ The data showed that endostatin could be successfully conjugated to the bifunctional chelator ethylenedicysteine (EC), and radiolabeled with technetium-99m and gallium-68, providing a unique opportunity to use a single precursor for both nuclear imaging modalities: 99mTc for single photon emission computed tomography and 68Ga for positron emission tomography, respectively. Both radiolabeled analogues showed increased binding as a function of time in human umbilical vein endothelial cells and mammary and prostate tumor cells. Binding could be blocked in a dose-dependent manner by unlabeled endostatin implying the presence of endostatin receptors on both vascular and tumor cells. Animal biodistribution studies demonstrated that both analogues were stable in vivo, showed typical reticuloendothelial and renal excretion and produced favorable absorbed organ doses for application in humans. The imaging data provide evidence that the compounds quantitate tumor volumes with clinically-useful tumor-to-nontumor ratios, and can be used for treatment follow-up to depict changes occurring at the vascular and cellular levels. ^ Two novel endostatin analogues were developed and demonstrated interaction with vascular and tumor cells. Both can be incorporated into existing nuclear imaging platforms allowing for potential wide-spread clinical benefit as well as serving as a diagnostic tool for elucidation of the mechanism of action of endostatin. ^

QKD in standard optical telecommunications networks

To perform Quantum Key Distribution, the mastering of the extremely weak signals carried by the quantum channel is required. Transporting these signals without disturbance is customarily done by isolating the quantum channel from any noise sources using a dedicated physical channel. However, to really profit from this technology, a full integration with conventional network technologies would be highly desirable. Trying to use single photon signals with others that carry an average power many orders of magnitude bigger while sharing as much infrastructure with a conventional network as possible brings obvious problems. The purpose of the present paper is to report our efforts in researching the limits of the integration of QKD in modern optical networks scenarios. We have built a full metropolitan area network testbed comprising a backbone and an access network. The emphasis is put in using as much as possible the same industrial grade technology that is actually used in already installed networks, in order to understand the throughput, limits and cost of deploying QKD in a real network.

Validación, caracterización y aplicación clínica en neuroimagen multimodalidad de técnicas de registro basadas en Teoría de la Información

La correcta validación y evaluación de cualquier algoritmo de registro incluido en la línea de procesamiento de cualquier aplicación clínica, es fundamental para asegurar la calidad y fiabilidad de los resultados obtenidos con ellas. Ambas características son imprescindibles, además, cuando dicha aplicación se encuentra en el área de la planificación quirúrgica, en la que las decisiones médicas influyen claramente en la invasividad sobre el paciente. El registro de imágenes es un proceso de alineamiento entre dos o más de éstas de forma que las características comunes se encuentren en el mismo punto del espacio. Este proceso, por tanto, se hace imprescindible en aquellas aplicaciones en las que existe la necesidad de combinar la información disponible en diferentes modalidades (fusión de imágenes) o bien la comparación de imágenes intra-modalidad tomadas de diferentes pacientes o en diferentes momentos. En el presente Trabajo Fin de Máster, se desarrolla un conjunto de herramientas para la evaluación de algoritmos de registro y se evalúan en la aplicación sobre imágenes multimodalidad a través de dos metodologías: 1) el uso de imágenes cuya alineación se conoce a priori a través de unos marcadores fiables (fiducial markers) eliminados de las imágenes antes del proceso de validación; y 2) el uso de imágenes sintetizadas con las propiedades de cierta modalidad de interés, generadas en base a otra modalidad objetivo y cuya des-alineación es controlada y conocida a priori. Para la primera de las metodologías, se hizo uso de un proyecto (RIRE – Retrospective Image Registration Evaluation Project) ampliamente conocido y que asegura la fiabilidad de la validación al realizarse por terceros. En la segunda, se propone la utilización de una metodología de simulación de imágenes SPECT (Single Photon Emission Computed Tomography) a partir de imágenes de Resonancia Magnética (que es la referencia anatómica). Finalmente, se realiza la modularización del algoritmo de registro validado en la herramienta FocusDET, para la localización del Foco Epileptógeno (FE) en Epilepsia parcial intratable, sustituyendo a la versión anterior en la que el proceso de registro se encontraba embebido en dicho software, dificultando enormemente cualquier tarea de revisión, validación o evaluación.

Non-destructive optical characterisation of fruits with time-resolved reflectance spectroscopy.

Increasing attention is being paid to the possible development of non-invasive tests for the assessment of the quality of fruits We propose a novel non-destructive method for the measurement of the internal optical properties of fruits and vegetables by means of time resolved reflectance spectroscopy in the visible and NIR range. A fully automated instrumentation for time-resolved reflectance measurements was developed It is based on mode-locked laser sources and electronics for time-correlated single photon counting, and provides a time-resolution of 120-160 ps The system was used to probe the optical properties of several species and varieties of fruits and vegetables in the red and NIR range (650-1000 nm). In most fruits, the absorption line shape is dominated by the absorption peak of water, centred around 970 nm Generally, the absorption spectra also show the spectral features typical of chlorophyll, with maximum at 675 nm In particular, for what concerns apples, variations in peak intensity are observed depending on the variety, the degree of ripeness as well as the position on the apple. For all the species and varieties considered, the transport scattering coefficient decreases progressively upon increasing the wavelength.

Non-destructive optical characterization of fruits in the red and near infrared.

Increasing attention is being paid to the possible development of non-invasive tests for the assessment of the quality of Fruits. We propose a novel non-destructive method for the measurement of the internal optical properties of fruits and vegetables by means of lime-resolved reflectance spectroscopy in the visible and NIR range. A Fully automated instrumentation for time-resolved reflectance measurements was developed. It is based on mode-locked laser sources and electronics for time-correlated single photon counting, and provides a time-resolution of 120-160 ps. The system was used to probe the optical properties of several species and varieties of Fruits and vegetables in the red and NIR range (650-1000 nm). In most Fruits, the absorption line shape is dominated by the absorption peak of water, centred around 970 nm. Generally, the absorption spectra also show the spectral features typical of chlorophyll, with maximum at 675 nm. In particular, for what concerns apples, variations in peak intensity are observed depending on the variety, the degree of ripeness as well as the position on the apple. For all the species and varieties considered, the transport scattering coefficient decreases progressively upon increasing the wavelength.

QuantiDOPA: A Quantification Software for Dopaminergic Neurotransmission SPECT

Quantification of neurotransmission Single-Photon Emission Computed Tomography (SPECT) studies of the dopaminergic system can be used to track, stage and facilitate early diagnosis of the disease. The aim of this study was to implement QuantiDOPA, a semi-automatic quantification software of application in clinical routine to reconstruct and quantify neurotransmission SPECT studies using radioligands which bind the dopamine transporter (DAT). To this end, a workflow oriented framework for the biomedical imaging (GIMIAS) was employed. QuantiDOPA allows the user to perform a semiautomatic quantification of striatal uptake by following three stages: reconstruction, normalization and quantification. QuantiDOPA is a useful tool for semi-automatic quantification inDAT SPECT imaging and it has revealed simple and flexible

Evaluación de ruido ambiental en las zonas de uso residencial ubicadas en la zona de influencia de la Avenida San Pablo (Barrio de la Estación, Coslada)

El presente documento analiza y evalúa el ruido ambiental existente en las zonas de uso residencial ubicadas en el Barrio de “La Estación”, en el entorno de la Avenida San Pablo, pertenecientes al municipio de Coslada (Madrid). La zona que contempla el proyecto es muy completa, ya que en ella están presentes diferentes tipos de ruido medioambiental (tráfico ferroviario, tráfico rodado, tráfico aeroportuario, ruido industrial de instalaciones, ruido de actividades, etc), donde las fuentes de ruido pueden manifestarse aisladas o en diversas combinaciones. Para evaluar el ruido total existente, se analiza por un lado el ruido residual de la zona de estudio, y por otro el ruido específico e intermitente asociado a sucesos aislados, como son el ruido de aviones y el ruido de trenes, donde se estudia individualmente la existencia de componentes de tonalidad, baja frecuencia e impulsividad. Una vez obtenidos los niveles de ruido total y ruido residual en la zona objeto de estudio, el índice Nivel de presión sonora promedio LPm de las muestras analizadas, estima correctamente los niveles obtenidos en el muestreo de larga duración. En las medidas realizadas se detecta la existencia de componentes de tonalidad y baja frecuencia en los pasos de aviones y trenes registrados. Se calculan los niveles sonoros existentes en la zona de estudio. Para ello se realiza una evaluación de los índices de ruido Ld, para el periodo día, y Le, para el periodo tarde, utilizando como herramienta de cálculo el programa IMMI 6.3.1e. Se realiza la validación del mapa de niveles sonoros obtenido con el IMMI 6.3.1e. Para ello se hace una comparación entre los niveles calculados con el modelo, y los niveles medidos “in situ” en los puntos de muestreo. Por último se obtiene la incertidumbre en cada una de las medidas ejecutadas en una segunda campaña “in situ”, correspondientes a niveles de presión sonora continuos equivalentes ponderado A (LAeq,5min), teniendo en cuenta las posibles desviaciones ocasionadas por el equipo de medida, condiciones meteorológicas, procedimiento de realización del ensayo, etc. ABSTRACT. The present document analyzes and evaluates the environmental noise in the residential areas located at “La Estación” district, near the San Pablo Avenue, in the Coslada municipality (Madrid). The area considered in this project is very complete, once it covers different types of environmental noise (railway traffic, vehicular traffic, airport traffic, industrial noise of building systems, activities noise, etc), where noise sources may appear isolated or under several combinations. In order to evaluate the existing total noise, on one hand it is analyzed the residual noise in the study area, and on the other hand it is analyzed the specific and intermittent noise associated to isolated occurrences, such as the noise of the aircrafts and the noise of the trains, where the existence of components of tonality, low frequency and impulsiveness is studied individually. After obtaining the levels of total noise and residual noise in the target study area, the sound pressure level average index (LPm) of the analyzed samples estimates correctly the levels obtained in the sampling of long duration. On what concerns the measures carried out, it is detected the existence of components of tonality and low frequency in the registered aircrafts and trains passage. The sound levels of the study area are calculated. For that it is made a valuation of the Ld noise ratio, concerning the day period, and Le, concerning the afternoon period. The calculation tool used is the IMMI 6.3.1e programme. The validation of the map of sound levels obtained with the IMMI 6.3.1e is made. In order to get this validation, it is made a comparison between the levels calculated with the model and the levels measured “in situ” in the sampling points. Finally the uncertainty is obtained in each one of the measurements made in a second sampling “in situ”, correspondent to equivalent A-weighted continuous sound pressure level (LAeq,5 min), having in mind the possible deviations caused by the equipment of measure, meteorological conditions, essay’s execution procedures, etc.

Molecular recognition with nanostructures fabricated by photopolymerization within metallic subwavelength apertures

The first demonstration of fabrication of submicron lateral resolution molecularly imprinted polymer (MIP) patterns by photoinduced local polymerization within metal subwavelength apertures is reported. The size of the photopolymerized MIP features is finely tuned by the dose of 532 nm radiation. Rhodamine 123 (R123) has been selected as a fluorescent model template to prove the recognition capability of the MIP nanostructures, which has been evaluated by fluorescence lifetime imaging microscopy (FLIM) with single photon timing measurements. The binding selectivity provided by the imprinting effect has been confirmed in the presence of compounds structurally related to R123. These results pave the way to the development of nanomaterial architectures with biomimetic artificial recognition properties for environmental, clinical and food testing.

NÃO PODEIS SERVIR A DEUS E ÀS RIQUEZAS: OS IMPACTOS ECONÔMICOS NO EVANGELHO DE MATEUS NO CONTEXTO DO JUDAÍSMO DO I SÉCULO

Esta pesquisa propõe um estudo do Evangelho produzido pela comunidade de Mateus, mais especificamente, o trabalho consiste em demonstrar a possibilidade de leitura desse evangelho a partir de implicações econômicas no seio da comunidade que o produziu. Entendemos o Evangelho de Mateus como um dos diversos movimentos judaicos do período pós-destruição do templo em 70 d.C.. Por causa desse contexto percebemos que o Evangelho de Mateus, debate com uma realidade de disputas religiosas desse período. É importante frisar que essas questões possuem vertentes e não terminam no âmbito religioso. As disputas religiosas conseqüentemente têm relações com todas as dimensões da vida, entre elas a econômica. Mateus resignifica para seu grupo a questão das posses, das riquezas, em virtude de uma realidade de crise econômica. E em meio a essa crise o Evangelho de Mateus, a partir de um trabalho redacional, dá novos significados à vida de fé da comunidade à luz das histórias de Jesus recebidas das fontes Marcos e Lucas. Este estudo justifica-se pela lacuna existente no material produzido sobre o Evangelho de Mateus, uma vez que o que é produzido a respeito dessas narrativas quase sempre se preocupa em analisar o conflito entre a comunidade de Mateus e os Fariseus somente no campo religioso deixando de lado as demais possibilidades, entre elas as relações econômicas.(AU)

NÃO PODEIS SERVIR A DEUS E ÀS RIQUEZAS: OS IMPACTOS ECONÔMICOS NO EVANGELHO DE MATEUS NO CONTEXTO DO JUDAÍSMO DO I SÉCULO

Esta pesquisa propõe um estudo do Evangelho produzido pela comunidade de Mateus, mais especificamente, o trabalho consiste em demonstrar a possibilidade de leitura desse evangelho a partir de implicações econômicas no seio da comunidade que o produziu. Entendemos o Evangelho de Mateus como um dos diversos movimentos judaicos do período pós-destruição do templo em 70 d.C.. Por causa desse contexto percebemos que o Evangelho de Mateus, debate com uma realidade de disputas religiosas desse período. É importante frisar que essas questões possuem vertentes e não terminam no âmbito religioso. As disputas religiosas conseqüentemente têm relações com todas as dimensões da vida, entre elas a econômica. Mateus resignifica para seu grupo a questão das posses, das riquezas, em virtude de uma realidade de crise econômica. E em meio a essa crise o Evangelho de Mateus, a partir de um trabalho redacional, dá novos significados à vida de fé da comunidade à luz das histórias de Jesus recebidas das fontes Marcos e Lucas. Este estudo justifica-se pela lacuna existente no material produzido sobre o Evangelho de Mateus, uma vez que o que é produzido a respeito dessas narrativas quase sempre se preocupa em analisar o conflito entre a comunidade de Mateus e os Fariseus somente no campo religioso deixando de lado as demais possibilidades, entre elas as relações econômicas.(AU)

Choroid plexus epithelial expression of MDR1 P glycoprotein and multidrug resistance-associated protein contribute to the blood–cerebrospinal-fluid drug-permeability barrier

The blood–brain barrier and a blood–cerebrospinal-fluid (CSF) barrier function together to isolate the brain from circulating drugs, toxins, and xenobiotics. The blood–CSF drug-permeability barrier is localized to the epithelium of the choroid plexus (CP). However, the molecular mechanisms regulating drug permeability across the CP epithelium are defined poorly. Herein, we describe a drug-permeability barrier in human and rodent CP mediated by epithelial-specific expression of the MDR1 (multidrug resistance) P glycoprotein (Pgp) and the multidrug resistance-associated protein (MRP). Noninvasive single-photon-emission computed tomography with 99mTc-sestamibi, a membrane-permeant radiopharmaceutical whose transport is mediated by both Pgp and MRP, shows a large blood-to-CSF concentration gradient across intact CP epithelium in humans in vivo. In rats, pharmacokinetic analysis with 99mTc-sestamibi determined the concentration gradient to be greater than 100-fold. In membrane fractions of isolated native CP from rat, mouse, and human, the 170-kDa Pgp and 190-kDa MRP are identified readily. Furthermore, the murine proteins are absent in CP isolated from their respective mdr1a/1b(−/−) and mrp(−/−) gene knockout littermates. As determined by immunohistochemical and drug-transport analysis of native CP and polarized epithelial cell cultures derived from neonatal rat CP, Pgp localizes subapically, conferring an apical-to-basal transepithelial permeation barrier to radiolabeled drugs. Conversely, MRP localizes basolaterally, conferring an opposing basal-to-apical drug-permeation barrier. Together, these transporters may coordinate secretion and reabsorption of natural product substrates and therapeutic drugs, including chemotherapeutic agents, antipsychotics, and HIV protease inhibitors, into and out of the central nervous system.

Fluorescence tomographic imaging in turbid media using early-arriving photons and Laplace transforms

We present a multichannel tomographic technique to detect fluorescent objects embedded in thick (6.4 cm) tissue-like turbid media using early-arriving photons. The experiments use picosecond laser pulses and a streak camera with single photon counting capability to provide short time resolution and high signal-to-noise ratio. The tomographic algorithm is based on the Laplace transform of an analytical diffusion approximation of the photon migration process and provides excellent agreement between the actual positions of the fluorescent objects and the experimental estimates. Submillimeter localization accuracy and 4- to 5-mm resolution are demonstrated. Moreover, objects can be accurately localized when fluorescence background is present. The results show the feasibility of using early-arriving photons to image fluorescent objects embedded in a turbid medium and its potential in clinical applications such as breast tumor detection.

Fluorescence microscopy with diffraction resolution barrier broken by stimulated emission

The diffraction barrier responsible for a finite focal spot size and limited resolution in far-field fluorescence microscopy has been fundamentally broken. This is accomplished by quenching excited organic molecules at the rim of the focal spot through stimulated emission. Along the optic axis, the spot size was reduced by up to 6 times beyond the diffraction barrier. The simultaneous 2-fold improvement in the radial direction rendered a nearly spherical fluorescence spot with a diameter of 90–110 nm. The spot volume of down to 0.67 attoliters is 18 times smaller than that of confocal microscopy, thus making our results also relevant to three-dimensional photochemistry and single molecule spectroscopy. Images of live cells reveal greater details.

Simultaneous two-photon excitation of distinct labels for dual-color fluorescence crosscorrelation analysis

Confocal fluorescence correlation spectroscopy as a time-averaging fluctuation analysis combining maximum sensitivity with high statistical confidence has proved to be a very versatile and powerful tool for detection and temporal investigation of biomolecules at ultralow concentrations on surfaces, in solutions, and in living cells. To probe the interaction of different molecular species for a detailed understanding of biologically relevant mechanisms, crosscorrelation studies on dual or multiple fluorophore assays with spectrally distinct excitation and emission are particularly promising. Despite the considerable improvement of detection specificity provided by fluorescence crosscorrelation analysis, few applications have so far been reported, presumably because of the practical challenges of properly aligning and controlling the stability of the experimental setup. In this work, we demonstrate that two-photon excitation combined with dual-color fluorescence correlation spectroscopy can be the key to simplifying simultaneous investigations of multiple fluorescent species significantly on a single-molecule scale. Two-photon excitation allows accession of common fluorophores of largely distinct emission by the same excitation wavelength, because differences in selection rules and vibronic coupling can induce considerable shifts between the one-photon and two-photon excitation spectra. The concept of dual-color two-photon fluorescence crosscorrelation analysis is introduced and experimentally demonstrated with an established assay probing the selective cleavage of dual-labeled DNA substrates by restriction endonuclease EcoRI.

Very-long-baseline radio interferometry (VLBI) observations of gamma-ray blazars: results from millimeter-VLBI observations.

VLBI observations of the extremely gamma-bright blazar PKS 0528+134 at 8, 22, 43, and 86 GHz reveal a strongly bent one-sided-core jet structure with at least three moving and two apparently stationary jet components. At the highest observing frequencies the brightest and most compact jet component (the VLBI core) is unresolved with an upper limit to its size of approximately 50 microarcsec corresponding to approximately 0.2 parsec [H0 = 100 km.s-1.Mpc-1 (megaparsec-1), q0 = 0.5, where H0 is Hubble constant and q0 is the deceleration parameter]. Two 86-GHz VLBI observations performed in 1993.3 and 1994.0 reveal a new jet component emerging with superluminal speed from the core. Linear back-extrapolation of its motion yields strong evidence that the ejection of this component is related to an outburst in the millimeter regime and a preceding intense flare of the gamma-flux density observed in early 1993. This and the radio/optical "light curves" and VLBI data for two other sources (S5 0836+710 and 3C 454.3) suggest that the observed gamma-radiation might be Doppler-boosted and perhaps is closely related to the physical processes acting near the "base" of the highly relativistic jets observed in quasars.