APPLICATIONS OF EPHB4 RECEPTOR SPECIFIC PEPTIDES IN TARGETED CANCER IMAGING AND THERAPY

EphB4 receptors, a member of the largest family of receptor tyrosine kinases, are found over-expressed in a variety of tumors cells including glioma cells as well as angiogenic blood vessels. Noninvasive imaging of EphB4 could potentially increase early detection rates, monitor response to therapy directed against EphB4, and improve patient outcomes. Targeted delivery of EphB4 receptor specific peptide conjugated hollow gold nanoshells (HAuNS) into tumors has great potential in cancer imaging and photothermal therapy. In this study, we developed an EphB4 specific peptide named TNYL-RAW and labeled with radioisotope 64Cu and Cy5.5 dye. We also conjugate this specific peptide with hollow gold nanoshells (HAuNS) to evaluate targeted photothermal therapy of cancers. In vitro, 64Cu-DOTA-TNYL- RAW specifically bind to CT26 and PC-3M cells but not to A549 cells. In vivo, Small-animal PET/CT clearly showed the significant uptake of 64Cu-DOTA-TNYL-RAW in CT26 and PC-3M tumors but not in A549 tumors. Furthermore, µPET/CT and near-infrared optical imaging clearly showed the uptake of the dual labeled TNYL-RAW peptide in both U251 and U87 tumors in the brains of nude mice. In U251 tumors, Cy5.5-labeled peptide can bind to EphB4-expressing tumor blood vessels and tumors cells. But in U87 models, dual labeled peptide only could bind to tumor associated blood vessels. Also, Irradiation of PC-3M and CT-26 cell treated with TNYL-PEG-HAuNS nanopatilces with near-infrared (NIR) laser resulted in selective destruction of these cells in vitro. EphB4 targeted TNYL-PEG-HAuNS showed more photothermal killing effect on CT26 tumor model than PEG-HAuNS did. In summary, tumors with overexpression of EphB4 receptors can be noninvasively visualized by micro PET/CT with 64Cu labeled or dual labeled TNYL-RAW peptide. Targeted delivery of TNYL-RAW conjugated HAuNS into tumors can greatly improve the treatment effect of photothermal therapy. The information acquired with this study should be advantageous in improving diagnostics and future applications in photothermal ablation therapy in clinical.

A Comparison of Radiocolloid and Indocyanine Green Fluorescence Imaging, Sentinel Lymph Node Mapping in Patients with Cervical Cancer Undergoing Laparoscopic Surgery.

BACKGROUND AND PURPOSE (99)TC combined with blue-dye mapping is considered the best sentinel lymph node (SLN) mapping technique in cervical cancer. Indocyanine green (ICG) with near infrared fluorescence imaging has been introduced as a new methodology for SLN mapping. The aim of this study was to compare these two techniques in the laparoscopic treatment of cervical cancer. METHODS Medical records of patients undergoing laparoscopic SLN mapping for cervical cancer with either (99)Tc and patent blue dye (Group 1) or ICG (Group 2) from April 2008 until August 2012 were reviewed. Sensitivity, specificity, and overall and bilateral detection rates were calculated and compared. RESULTS Fifty-eight patients were included in the study-36 patients in Group 1 and 22 patients in Group 2. Median tumor diameter was 25 and 29 mm, and mean SLN count was 2.1 and 3.7, for Groups 1 and 2, respectively. Mean non-SLN (NSLN) count was 39 for both groups. SLNs were ninefold more likely to be affected by metastatic disease compared with NSLNs (p < 0.005). Sensitivity and specificity were both 100 %. Overall detection rates were 83 and 95.5 % (p = nonsignificant), and bilateral detection rates were 61 and 95.5 % (p < 0.005), for Groups 1 and 2, respectively. In 75 % of cases, SLNs were located along the external or internal iliac nodal basins. CONCLUSIONS ICG SLN mapping in cervical cancer provides high overall and bilateral detection rates that compare favorably with the current standard of care.

Fractures on comet 67P/Churyumov-Gerasimenko observed by Rosetta/OSIRIS

The Optical, Spectroscopic, and Infrared Remote Imaging System (OSIRIS) experiment onboard the Rosetta spacecraft currently orbiting comet 67P/Churyumov-Gerasimenko has yielded unprecedented views of a comet's nucleus. We present here the first ever observations of meter-scale fractures on the surface of a comet. Some of these fractures form polygonal networks. We present an initial assessment of their morphology, topology, and regional distribution. Fractures are ubiquitous on the surface of the comet's nucleus. Furthermore, they occur in various settings and show different topologies suggesting numerous formation mechanisms, which include thermal insulation weathering, orbital-induced stresses, and possibly seasonal thermal contraction. However, we conclude that thermal insolation weathering is responsible for creating most of the observed fractures based on their morphology and setting in addition to thermal models that indicate diurnal temperature ranges exceeding 200K and thermal gradients of similar to 15K/min at perihelion are possible. Finally, we suggest that fractures could be a facilitator in surface evolution and long-term erosion.

Reconocimiento de objetos a partir de imágenes termográficas

La termografía es un método de inspección y diagnóstico basado en la radiación infrarroja que emiten los cuerpos. Permite medir dicha radiación a distancia y sin contacto, obteniendo un termograma o imagen termográfica, objeto de estudio de este proyecto. Todos los cuerpos que se encuentren a una cierta temperatura emiten radiación infrarroja. Sin embargo, para hacer una inspección termográfica hay que tener en cuenta la emisividad de los cuerpos, capacidad que tienen de emitir radiación, ya que ésta no sólo depende de la temperatura del cuerpo, sino también de sus características superficiales. Las herramientas necesarias para conseguir un termograma son principalmente una cámara termográfica y un software que permita su análisis. La cámara percibe la emisión infrarroja de un objeto y lo convierte en una imagen visible, originalmente monocromática. Sin embargo, después es coloreada por la propia cámara o por un software para una interpretación más fácil del termograma. Para obtener estas imágenes termográficas existen varias técnicas, que se diferencian en cómo la energía calorífica se transfiere al cuerpo. Estas técnicas se clasifican en termografía pasiva, activa y vibrotermografía. El método que se utiliza en cada caso depende de las características térmicas del cuerpo, del tipo de defecto a localizar o la resolución espacial de las imágenes, entre otros factores. Para analizar las imágenes y así obtener diagnósticos y detectar defectos, es importante la precisión. Por ello existe un procesado de las imágenes, para minimizar los efectos provocados por causas externas, mejorar la calidad de la imagen y extraer información de las inspecciones realizadas. La termografía es un método de ensayo no destructivo muy flexible y que ofrece muchas ventajas. Por esta razón el campo de aplicación es muy amplio, abarcando desde aplicaciones industriales hasta investigación y desarrollo. Vigilancia y seguridad, ahorro energético, medicina o medio ambiente, son algunos de los campos donde la termografía aportaimportantes beneficios. Este proyecto es un estudio teórico de la termografía, donde se describen detalladamente cada uno de los aspectos mencionados. Concluye con una aplicación práctica, creando una cámara infrarroja a partir de una webcam, y realizando un análisis de las imágenes obtenidas con ella. Con esto se demuestran algunas de las teorías explicadas, así como la posibilidad de reconocer objetos mediante la termografía. Thermography is a method of testing and diagnosis based on the infrared radiation emitted by bodies. It allows to measure this radiation from a distance and with no contact, getting a thermogram or thermal image, object of study of this project. All bodies that are at a certain temperature emit infrared radiation. However, making a thermographic inspection must take into account the emissivity of the body, capability of emitting radiation. This not only depends on the temperature of the body, but also on its surface characteristics. The tools needed to get a thermogram are mainly a thermal imaging camera and software that allows analysis. The camera sees the infrared emission of an object and converts it into a visible image, originally monochrome. However, after it is colored by the camera or software for easier interpretation of thermogram. To obtain these thermal images it exists various techniques, which differ in how heat energy is transferred to the body. These techniques are classified into passive thermography, active and vibrotermografy. The method used in each case depends on the thermal characteristics of the body, the type of defect to locate or spatial resolution of images, among other factors. To analyze the images and obtain diagnoses and defects, accuracy is important. Thus there is a image processing to minimize the effects caused by external causes, improving image quality and extract information from inspections. Thermography is a non-­‐destructive test method very flexible and offers many advantages. So the scope is very wide, ranging from industrial applications to research and development.Surveillance and security, energy saving, environmental or medicine are some of the areas where thermography provides significant benefits. This project is a theoretical study of thermography, which describes in detail each of these aspects. It concludes with a practical application, creating an infrared camera from a webcam, and making an analysis of the images obtained with it. This will demonstrate some of the theories explained as well as the ability to recognize objects by thermography.

Use of thermographic imaging to screen for drought-tolerant genotypes in Brachypodium distachyon

Thermal imaging has been used to evaluate the response to drought and warm temperatures in a collection of Brachypodium distachyon lines adapted to varied environmental conditions. Thermographic records were able to separate lines from contrasting rainfall regimes. Genotypes from dryer environments showed warmer leaves under water deficit, which suggested that decreased evapotranspiration was related to a more intense stomatal closure. When irrigated and under high temperature conditions, drought-adapted lines showed cooler leaves than lines from wetter zones. The consistent, inverse thermographic response of lines to water stress and heat validates the reliability of this method to assess drought tolerance in this model cereal. It additionally supports the hypothesis that stomatal-based mechanisms are involved in natural variation for drought tolerance in Brachypodium. The study further suggests that these mechanisms are not constitutive but likely related to a more efficient closing response to avoid dehydration in adapted genotypes. Higher leaf temperature under water deficit seems a dependable criterion of drought tolerance, not only in B. distachyon but also in the main cereal crops and related grasses where thermography can facilitate high-throughput preliminary screening of tolerant materials.

The combined impact of urban heat island, thermal bridge effect of buildings and future climate change on the potential overwintering of Phlebotomus species in a Central European metropolis

Leishmaniasis is one of the most important emerging vector-borne diseases in Western Eurasia. Although winter minimum temperatures limit the present geographical distribution of the vector Phlebotomus species, the heat island effect of the cities and the anthropogenic heat emission together may provide the appropriate environment for the overwintering of sand flies. We studied the climate tempering effect of thermal bridges and the heat island effect in Budapest, Hungary. Thermal imaging was used to measure the heat surplus of heat bridges. The winter heat island effect of the city was evaluated by numerical analysis of the measurements of the Aqua sensor of satellite Terra. We found that the surface temperature of thermal bridges can be at least 3-7 °C higher than the surrounding environment. The heat emission of thermal bridges and the urban heat island effect together can cause at least 10 °C higher minimum ambient temperature in winter nights than the minimum temperature of the peri-urban areas. This milder micro-climate of the built environment can enable the potential overwintering of some important European Phlebotomus species. The anthropogenic heat emission of big cities may explain the observed isolated northward populations of Phlebotomus ariasi in Paris and Phlebotomus neglectus in the agglomeration of Budapest.

Thermal measurements on sub-Antarctic megaherbs and environmental characteristics on Campbell Island in 2010

We evaluated whether heating occurs in sub-Antarctic megaherbs, and the relation of heating to relevant environmental variables. We measured leaf and inflorescence temperature in six sub-Antarctic megaherb species on Campbell Island, latitude 52.3°S, New Zealand Biological Region. Using thermal imaging camera (Fluke TI20, http://www.fluke.com/fluke/caen/support/software/ti-update) and thermal probe (Fluke 51 II digital thermal probe), in combination with measurement of solar radiation, ambient air temperature, wind speed, wind chill and humidity.

Sinthesys of heteroleptic zinc complexes for imaging in living cells

This thesis arose from an interest in luminescence heteroleptic bis(dipyrrinato) Zn (II) complexes and their application in cell imaging, due to their attractive and fascinating characteristics. Among imaging technologies, near-infrared fluorescence imaging has been dedicated immense attention owing to its low absorption and autofluorescence from surrounding organism and tissues in this specific spectral region, which minimize background interference and improve tissue depth penetration. An ideal near-infrared probe should be equipped with excellence chemical and photophysical properties. The target of this work is the synthesis of new heteroleptic bis(dipyrrinato) Zn (II) complexes having two main features: the emission in the near-infrared region and water-solubility. In order to purse these intentions, the low-energy emission was achieved by expansion of π-conjugation of simple dipyrrins using Knoevenagel condensation106 and tri(ethylene)glycol chain was introduced to increase the water solubility of the final complex. Photophysical and luminescent properties of the new complexes were investigated. Finally, with a view to a potential biological use of these new complexes in biological environments, their biocompatibility was tested using a cell viability assay: (3-(4,5-dimethylthiazol-2-yl)-2’-5’-diphenyltetrazolium bromide (MTT) assay.

Behavioral and Autonomic Responses to Acute Restraint Stress Are Segregated within the Lateral Septal Area of Rats

Background: The Lateral Septal Area (LSA) is involved with autonomic and behavior responses associated to stress. In rats, acute restraint (RS) is an unavoidable stress situation that causes autonomic (body temperature, mean arterial pressure (MAP) and heart rate (HR) increases) and behavioral (increased anxiety-like behavior) changes in rats. The LSA is one of several brain regions that have been involved in stress responses. The aim of the present study was to investigate if the neurotransmission blockade in the LSA would interfere in the autonomic and behavioral changes induced by RS. Methodology/Principal Findings: Male Wistar rats with bilateral cannulae aimed at the LSA, an intra-abdominal datalogger (for recording internal body temperature), and an implanted catheter into the femoral artery (for recording and cardiovascular parameters) were used. They received bilateral microinjections of the non-selective synapse blocker cobalt chloride (CoCl(2), 1 mM/ 100 nL) or vehicle 10 min before RS session. The tail temperature was measured by an infrared thermal imager during the session. Twenty-four h after the RS session the rats were tested in the elevated plus maze (EPM). Conclusions/Significance: Inhibition of LSA neurotransmission reduced the MAP and HR increases observed during RS. However, no changes were observed in the decrease in skin temperature and increase in internal body temperature observed during this period. Also, LSA inhibition did not change the anxiogenic effect induced by RS observed 24 h later in the EPM. The present results suggest that LSA neurotransmission is involved in the cardiovascular but not the temperature and behavioral changes induced by restraint stress.