Thermoelectric assessment of laser peening induced effects on a metallic biomedical Ti6Al4V

Laser peening has recently emerged as a useful technique to overcome detrimental effects associated to another well-known surface modification processes such as shot peening or grit blasting used in the biomedical field. It is worth to notice that besides the primary residual stress effect, thermally induced effects might also cause subtle surface and subsurface microstructural changes that might influence corrosion resistance. Moreover, since maximum loads use to occur at the surface, they could also play a critical role in the fatigue strength. In this work, plates of Ti-6Al-4V alloy of 7 mm in thickness were modified by laser peening without using a sacrificial outer layer. Irradiation by a Q-switched Nd-YAG laser (9.4 ns pulse length) working in fundamental harmonic at 2.8 J/pulse and with water as confining medium was used. Laser pulses with a 1.5 mm diameter at an equivalent overlapping density (EOD) of 5000 cm-2 were applied. Attempts to analyze the global induced effects after laser peening were addressed by using the contacting and non-contacting thermoelectric power (TEP) techniques. It was demonstrated that the thermoelectric method is entirely insensitive to surface topography while it is uniquely sensitive to subtle variations in thermoelectric properties, which are associated with the different material effects induced by different surface modification treatments. These results indicate that the stress-dependence of the thermoelectric power in metals produces sufficient contrast to detect and quantitatively characterize regions under compressive residual stress based on their thermoelectric power contrast with respect to the surrounding intact material. However, further research is needed to better separate residual stress effects from secondary material effects, especially in the case of low-conductivity engineering materials like titanium alloys.

Sistema para integrar automáticamente datos públicos del NCBI en la plataforma de medicina personalizada p-medicine

En los últimos años ha habido un gran aumento de fuentes de datos biomédicos. La aparición de nuevas técnicas de extracción de datos genómicos y generación de bases de datos que contienen esta información ha creado la necesidad de guardarla para poder acceder a ella y trabajar con los datos que esta contiene. La información contenida en las investigaciones del campo biomédico se guarda en bases de datos. Esto se debe a que las bases de datos permiten almacenar y manejar datos de una manera simple y rápida. Dentro de las bases de datos existen una gran variedad de formatos, como pueden ser bases de datos en Excel, CSV o RDF entre otros. Actualmente, estas investigaciones se basan en el análisis de datos, para a partir de ellos, buscar correlaciones que permitan inferir, por ejemplo, tratamientos nuevos o terapias más efectivas para una determinada enfermedad o dolencia. El volumen de datos que se maneja en ellas es muy grande y dispar, lo que hace que sea necesario el desarrollo de métodos automáticos de integración y homogeneización de los datos heterogéneos. El proyecto europeo p-medicine (FP7-ICT-2009-270089) tiene como objetivo asistir a los investigadores médicos, en este caso de investigaciones relacionadas con el cáncer, proveyéndoles con nuevas herramientas para el manejo de datos y generación de nuevo conocimiento a partir del análisis de los datos gestionados. La ingestión de datos en la plataforma de p-medicine, y el procesamiento de los mismos con los métodos proporcionados, buscan generar nuevos modelos para la toma de decisiones clínicas. Dentro de este proyecto existen diversas herramientas para integración de datos heterogéneos, diseño y gestión de ensayos clínicos, simulación y visualización de tumores y análisis estadístico de datos. Precisamente en el ámbito de la integración de datos heterogéneos surge la necesidad de añadir información externa al sistema proveniente de bases de datos públicas, así como relacionarla con la ya existente mediante técnicas de integración semántica. Para resolver esta necesidad se ha creado una herramienta, llamada Term Searcher, que permite hacer este proceso de una manera semiautomática. En el trabajo aquí expuesto se describe el desarrollo y los algoritmos creados para su correcto funcionamiento. Esta herramienta ofrece nuevas funcionalidades que no existían dentro del proyecto para la adición de nuevos datos provenientes de fuentes públicas y su integración semántica con datos privados.---ABSTRACT---Over the last few years, there has been a huge growth of biomedical data sources. The emergence of new techniques of genomic data generation and data base generation that contain this information, has created the need of storing it in order to access and work with its data. The information employed in the biomedical research field is stored in databases. This is due to the capability of databases to allow storing and managing data in a quick and simple way. Within databases there is a variety of formats, such as Excel, CSV or RDF. Currently, these biomedical investigations are based on data analysis, which lead to the discovery of correlations that allow inferring, for example, new treatments or more effective therapies for a specific disease or ailment. The volume of data handled in them is very large and dissimilar, which leads to the need of developing new methods for automatically integrating and homogenizing the heterogeneous data. The p-medicine (FP7-ICT-2009-270089) European project aims to assist medical researchers, in this case related to cancer research, providing them with new tools for managing and creating new knowledge from the analysis of the managed data. The ingestion of data into the platform and its subsequent processing with the provided tools aims to enable the generation of new models to assist in clinical decision support processes. Inside this project, there exist different tools related to areas such as the integration of heterogeneous data, the design and management of clinical trials, simulation and visualization of tumors and statistical data analysis. Particularly in the field of heterogeneous data integration, there is a need to add external information from public databases, and relate it to the existing ones through semantic integration methods. To solve this need a tool has been created: the term Searcher. This tool aims to make this process in a semiautomatic way. This work describes the development of this tool and the algorithms employed in its operation. This new tool provides new functionalities that did not exist inside the p-medicine project for adding new data from public databases and semantically integrate them with private data.

Design and development of compact optical systems = Diseño y desarrollo de sistemas ópticos compactos

Esta tesis considera dos tipos de aplicaciones del diseño óptico: óptica formadora de imagen por un lado, y óptica anidólica (nonimaging) o no formadora de imagen, por otro. Las ópticas formadoras de imagen tienen como objetivo la obtención de imágenes de puntos del objeto en el plano de la imagen. Por su parte, la óptica anidólica, surgida del desarrollo de aplicaciones de concentración e iluminación, se centra en la transferencia de energía en forma de luz de forma eficiente. En general, son preferibles los diseños ópticos que den como resultado sistemas compactos, para ambos tipos de ópticas (formadora de imagen y anidólica). En el caso de los sistemas anidólicos, una óptica compacta permite tener costes de producción reducidos. Hay dos razones: (1) una óptica compacta presenta volúmenes reducidos, lo que significa que se necesita menos material para la producción en masa; (2) una óptica compacta es pequeña y ligera, lo que ahorra costes en el transporte. Para los sistemas ópticos de formación de imagen, además de las ventajas anteriores, una óptica compacta aumenta la portabilidad de los dispositivos, que es una gran ventaja en tecnologías de visualización portátiles, tales como cascos de realidad virtual (HMD del inglés Head Mounted Display). Esta tesis se centra por tanto en nuevos enfoques de diseño de sistemas ópticos compactos para aplicaciones tanto de formación de imagen, como anidólicas. Los colimadores son uno de los diseños clásicos dentro la óptica anidólica, y se pueden utilizar en aplicaciones fotovoltaicas y de iluminación. Hay varios enfoques a la hora de diseñar estos colimadores. Los diseños convencionales tienen una relación de aspecto mayor que 0.5. Con el fin de reducir la altura del colimador manteniendo el área de iluminación, esta tesis presenta un diseño de un colimador multicanal. En óptica formadora de imagen, las superficies asféricas y las superficies sin simetría de revolución (o freeform) son de gran utilidad de cara al control de las aberraciones de la imagen y para reducir el número y tamaño de los elementos ópticos. Debido al rápido desarrollo de sistemas de computación digital, los trazados de rayos se pueden realizar de forma rápida y sencilla para evaluar el rendimiento del sistema óptico analizado. Esto ha llevado a los diseños ópticos modernos a ser generados mediante el uso de diferentes técnicas de optimización multi-paramétricas. Estas técnicas requieren un buen diseño inicial como punto de partida para el diseño final, que será obtenido tras un proceso de optimización. Este proceso precisa un método de diseño directo para superficies asféricas y freeform que den como resultado un diseño cercano al óptimo. Un método de diseño basado en ecuaciones diferenciales se presenta en esta tesis para obtener un diseño óptico formado por una superficie freeform y dos superficies asféricas. Esta tesis consta de cinco capítulos. En Capítulo 1, se presentan los conceptos básicos de la óptica formadora de imagen y de la óptica anidólica, y se introducen las técnicas clásicas del diseño de las mismas. El Capítulo 2 describe el diseño de un colimador ultra-compacto. La relación de aspecto ultra-baja de este colimador se logra mediante el uso de una estructura multicanal. Se presentará su procedimiento de diseño, así como un prototipo fabricado y la caracterización del mismo. El Capítulo 3 describe los conceptos principales de la optimización de los sistemas ópticos: función de mérito y método de mínimos cuadrados amortiguados. La importancia de un buen punto de partida se demuestra mediante la presentación de un mismo ejemplo visto a través de diferentes enfoques de diseño. El método de las ecuaciones diferenciales se presenta como una herramienta ideal para obtener un buen punto de partida para la solución final. Además, diferentes técnicas de interpolación y representación de superficies asféricas y freeform se presentan para el procedimiento de optimización. El Capítulo 4 describe la aplicación del método de las ecuaciones diferenciales para un diseño de un sistema óptico de una sola superficie freeform. Algunos conceptos básicos de geometría diferencial son presentados para una mejor comprensión de la derivación de las ecuaciones diferenciales parciales. También se presenta un procedimiento de solución numérica. La condición inicial está elegida como un grado de libertad adicional para controlar la superficie donde se forma la imagen. Basado en este enfoque, un diseño anastigmático se puede obtener fácilmente y se utiliza como punto de partida para un ejemplo de diseño de un HMD con una única superficie reflectante. Después de la optimización, dicho diseño muestra mejor rendimiento. El Capítulo 5 describe el método de las ecuaciones diferenciales ampliado para diseños de dos superficies asféricas. Para diseños ópticos de una superficie, ni la superficie de imagen ni la correspondencia entre puntos del objeto y la imagen pueden ser prescritas. Con esta superficie adicional, la superficie de la imagen se puede prescribir. Esto conduce a un conjunto de tres ecuaciones diferenciales ordinarias implícitas. La solución numérica se puede obtener a través de cualquier software de cálculo numérico. Dicho procedimiento también se explica en este capítulo. Este método de diseño da como resultado una lente anastigmática, que se comparará con una lente aplanática. El diseño anastigmático converge mucho más rápido en la optimización y la solución final muestra un mejor rendimiento. ABSTRACT We will consider optical design from two points of view: imaging optics and nonimaging optics. Imaging optics focuses on the imaging of the points of the object. Nonimaging optics arose from the development of concentrators and illuminators, focuses on the transfer of light energy, and has wide applications in illumination and concentration photovoltaics. In general, compact optical systems are necessary for both imaging and nonimaging designs. For nonimaging optical systems, compact optics use to be important for reducing cost. The reasons are twofold: (1) compact optics is small in volume, which means less material is needed for mass-production; (2) compact optics is small in size and light in weight, which saves cost in transportation. For imaging optical systems, in addition to the above advantages, compact optics increases portability of devices as well, which contributes a lot to wearable display technologies such as Head Mounted Displays (HMD). This thesis presents novel design approaches of compact optical systems for both imaging and nonimaging applications. Collimator is a typical application of nonimaging optics in illumination, and can be used in concentration photovoltaics as well due to the reciprocity of light. There are several approaches for collimator designs. In general, all of these approaches have an aperture diameter to collimator height not greater than 2. In order to reduce the height of the collimator while maintaining the illumination area, a multichannel design is presented in this thesis. In imaging optics, aspheric and freeform surfaces are useful in controlling image aberrations and reducing the number and size of optical elements. Due to the rapid development of digital computing systems, ray tracing can be easily performed to evaluate the performance of optical system. This has led to the modern optical designs created by using different multi-parametric optimization techniques. These techniques require a good initial design to be a starting point so that the final design after optimization procedure can reach the optimum solution. This requires a direct design method for aspheric and freeform surface close to the optimum. A differential equation based design method is presented in this thesis to obtain single freeform and double aspheric surfaces. The thesis comprises of five chapters. In Chapter 1, basic concepts of imaging and nonimaging optics are presented and typical design techniques are introduced. Readers can obtain an understanding for the following chapters. Chapter 2 describes the design of ultra-compact collimator. The ultra-low aspect ratio of this collimator is achieved by using a multichannel structure. Its design procedure is presented together with a prototype and its evaluation. The ultra-compactness of the device has been approved. Chapter 3 describes the main concepts of optimizing optical systems: merit function and Damped Least-Squares method. The importance of a good starting point is demonstrated by presenting an example through different design approaches. The differential equation method is introduced as an ideal tool to obtain a good starting point for the final solution. Additionally, different interpolation and representation techniques for aspheric and freeform surface are presented for optimization procedure. Chapter 4 describes the application of differential equation method in the design of single freeform surface optical system. Basic concepts of differential geometry are presented for understanding the derivation of partial differential equations. A numerical solution procedure is also presented. The initial condition is chosen as an additional freedom to control the image surface. Based on this approach, anastigmatic designs can be readily obtained and is used as starting point for a single reflective surface HMD design example. After optimization, the evaluation shows better MTF. Chapter 5 describes the differential equation method extended to double aspheric surface designs. For single optical surface designs, neither image surface nor the mapping from object to image can be prescribed. With one more surface added, the image surface can be prescribed. This leads to a set of three implicit ordinary differential equations. Numerical solution can be obtained by MATLAB and its procedure is also explained. An anastigmatic lens is derived from this design method and compared with an aplanatic lens. The anastigmatic design converges much faster in optimization and the final solution shows better performance.

Functional identification and reconstitution of an odorant receptor in single olfactory neurons

The olfactory system is remarkable in its capacity to discriminate a wide range of odorants through a series of transduction events initiated in olfactory receptor neurons. Each olfactory neuron is expected to express only a single odorant receptor gene that belongs to the G protein coupled receptor family. The ligand–receptor interaction, however, has not been clearly characterized. This study demonstrates the functional identification of olfactory receptor(s) for specific odorant(s) from single olfactory neurons by a combination of Ca2+-imaging and reverse transcription–coupled PCR analysis. First, a candidate odorant receptor was cloned from a single tissue-printed olfactory neuron that displayed odorant-induced Ca2+ increase. Next, recombinant adenovirus-mediated expression of the isolated receptor gene was established in the olfactory epithelium by using green fluorescent protein as a marker. The infected neurons elicited external Ca2+ entry when exposed to the odorant that originally was used to identify the receptor gene. Experiments performed to determine ligand specificity revealed that the odorant receptor recognized specific structural motifs within odorant molecules. The odorant receptor-mediated signal transduction appears to be reconstituted by this two-step approach: the receptor screening for given odorant(s) from single neurons and the functional expression of the receptor via recombinant adenovirus. The present approach should enable us to examine not only ligand specificity of an odorant receptor but also receptor specificity and diversity for a particular odorant of interest.

Membrane voltage initiates Ca2+ waves and potentiates Ca2+ increases with abscisic acid in stomatal guard cells

In higher plants changes and oscillations in cytosolic free Ca2+ concentration ([Ca2+]i) are central to hormonal physiology, including that of abscisic acid (ABA), which signals conditions of water stress and alters ion channel activities in guard cells of higher-plant leaves. Such changes in [Ca2+]i are thought to encode for cellular responses to different stimuli, but their origins and functions are poorly understood. Because transients and oscillations in membrane voltage also occur in guard cells and are elicited by hormones, including ABA, we suspected a coupling of [Ca2+]i to voltage and its interaction with ABA. We recorded [Ca2+]i by Fura2 fluorescence ratio imaging and photometry while bringing membrane voltage under experimental control with a two-electrode voltage clamp in intact Vicia guard cells. Free-running oscillations between voltages near −50 mV and −200 mV were associated with oscillations in [Ca2+]i, and, under voltage clamp, equivalent membrane hyperpolarizations caused [Ca2+]i to increase, often in excess of 1 μM, from resting values near 100 nM. Image analysis showed that the voltage stimulus evoked a wave of high [Ca2+]i that spread centripetally from the peripheral cytoplasm within 5–10 s and relaxed over 40–60 s thereafter. The [Ca2+]i increases showed a voltage threshold near −120 mV and were sensitive to external Ca2+ concentration. Substituting Mn2+ for Ca2+ to quench Fura2 fluorescence showed that membrane hyperpolarization triggered a divalent influx. ABA affected the voltage threshold for the [Ca2+]i rise, its amplitude, and its duration. In turn, membrane voltage determined the ability of ABA to raise [Ca2+]i. These results demonstrate a capacity for voltage to evoke [Ca2+]i increases, they point to a dual interaction with ABA in triggering and propagating [Ca2+]i increases, and they implicate a role for voltage in “conditioning” [Ca2+]i signals that regulate ion channels for stomatal function.

Design and characterization of α-melanotropin peptide analogs cyclized through rhenium and technetium metal coordination

α-Melanocyte stimulating hormone (α-MSH) analogs, cyclized through site-specific rhenium (Re) and technetium (Tc) metal coordination, were structurally characterized and analyzed for their abilities to bind α-MSH receptors present on melanoma cells and in tumor-bearing mice. Results from receptor-binding assays conducted with B16 F1 murine melanoma cells indicated that receptor-binding affinity was reduced to approximately 1% of its original levels after Re incorporation into the cyclic Cys4,10, d-Phe7–α-MSH4-13 analog. Structural analysis of the Re–peptide complex showed that the disulfide bond of the original peptide was replaced by thiolate–metal–thiolate cyclization. A comparison of the metal-bound and metal-free structures indicated that metal complexation dramatically altered the structure of the receptor-binding core sequence. Redesign of the metal binding site resulted in a second-generation Re–peptide complex (ReCCMSH) that displayed a receptor-binding affinity of 2.9 nM, 25-fold higher than the initial Re–α-MSH analog. Characterization of the second-generation Re–peptide complex indicated that the peptide was still cyclized through Re coordination, but the structure of the receptor-binding sequence was no longer constrained. The corresponding 99mTc- and 188ReCCMSH complexes were synthesized and shown to be stable in phosphate-buffered saline and to challenges from diethylenetriaminepentaacetic acid (DTPA) and free cysteine. In vivo, the 99mTcCCMSH complex exhibited significant tumor uptake and retention and was effective in imaging melanoma in a murine-tumor model system. Cyclization of α-MSH analogs via 99mTc and 188Re yields chemically stable and biologically active molecules with potential melanoma-imaging and therapeutic properties.

Localization of the N terminus of hepatitis B virus capsid protein by peptide-based difference mapping from cryoelectron microscopy

Recently, cryoelectron microscopy of isolated macromolecular complexes has advanced to resolutions below 10 Å, enabling direct visualization of α-helical secondary structure. To help correlate such density maps with the amino acid sequences of the component proteins, we advocate peptide-based difference mapping, i.e., insertion of peptides, ≈10 residues long, at targeted points in the sequence and visualization of these peptides as bulk labels in cryoelectron microscopy-derived difference maps. As proof of principle, we have appended an extraneous octapeptide at the N terminus of hepatitis B virus capsid protein and determined its location on the capsid surface by difference imaging at 11 Å resolution. Hepatitis B virus capsids are icosahedral particles, ≈300 Å in diameter, made up of T-shaped dimers (subunit Mr, 16–21 kDa, depending on construct). The stems of the Ts protrude outward as spikes, whereas the crosspieces pack to form the contiguous shell. The two N termini per dimer reside on either side of the spike-stem, at the level at which it enters the shell. This location is consistent with formation of the known intramolecular disulfide bond between the cysteines at positions 61 and −7 (in the residual propeptide) in the “e-antigen” form of the capsid protein and has implications for why this clinically important antigen remains unassembled in vivo.

Vascular imprints of neuronal activity: Relationships between the dynamics of cortical blood flow, oxygenation, and volume changes following sensory stimulation

Modern functional neuroimaging methods, such as positron-emission tomography (PET), optical imaging of intrinsic signals, and functional MRI (fMRI) utilize activity-dependent hemodynamic changes to obtain indirect maps of the evoked electrical activity in the brain. Whereas PET and flow-sensitive MRI map cerebral blood flow (CBF) changes, optical imaging and blood oxygenation level-dependent MRI map areas with changes in the concentration of deoxygenated hemoglobin (HbR). However, the relationship between CBF and HbR during functional activation has never been tested experimentally. Therefore, we investigated this relationship by using imaging spectroscopy and laser-Doppler flowmetry techniques, simultaneously, in the visual cortex of anesthetized cats during sensory stimulation. We found that the earliest microcirculatory change was indeed an increase in HbR, whereas the CBF increase lagged by more than a second after the increase in HbR. The increased HbR was accompanied by a simultaneous increase in total hemoglobin concentration (Hbt), presumably reflecting an early blood volume increase. We found that the CBF changes lagged after Hbt changes by 1 to 2 sec throughout the response. These results support the notion of active neurovascular regulation of blood volume in the capillary bed and the existence of a delayed, passive process of capillary filling.

Ethidium derivatives bind to G-quartets, inhibit telomerase and act as fluorescent probes for quadruplexes

The telomeric G-rich single-stranded DNA can adopt in vitro an intramolecular quadruplex structure, which has been shown to directly inhibit telomerase activity. The reactivation of this enzyme in immortalized and most cancer cells suggests that telomerase is a relevant target in oncology, and telomerase inhibitors have been proposed as new potential anticancer agents. In this paper, we describe ethidium derivatives that stabilize G-quadruplexes. These molecules were shown to increase the melting temperature of an intramolecular quadruplex structure, as shown by fluorescence and absorbance measurements, and to facilitate the formation of intermolecular quadruplex structures. In addition, these molecules may be used to reveal the formation of multi-stranded DNA structures by standard fluorescence imaging, and therefore become fluorescent probes of quadruplex structures. This recognition was associated with telomerase inhibition in vitro: these derivatives showed a potent anti-telomerase activity, with IC50 values of 18–100 nM in a standard TRAP assay.

Republican Scientific-Medical Library, The Republic of Armenia: progress and programs*

In 1990, the Republican Scientific-Medical Library (RSML) of the Ministry of Health of Armenia in collaboration with the Fund for Armenian Relief created a vision of a national library network supported by information technology. This vision incorporated four goals: (1) to develop a national resource collection of biomedical literature accessible to all health professionals, (2) to develop a national network for access to bibliographic information, (3) to develop a systematic mechanism for sharing resources, and (4) to develop a national network of health sciences libraries. During the last decade, the RSML has achieved significant progress toward all four goals and has realized its vision of becoming a fully functional national library. The RSML now provides access to the literature of the health sciences including access to the Armenian medical literature, provides education and training to health professionals and health sciences librarians, and manages a national network of libraries of the major health care institutions in Armenia. The RSML is now able to provide rapid access to the biomedical literature and train health professionals and health sciences librarians in Armenia in information system use. This paper describes the evolution of the RSML and how it was accomplished.

X-ray emission from clusters and groups of galaxies

Recent major advances in x-ray imaging and spectroscopy of clusters have allowed the determination of their mass and mass profile out to ≈1/2 the virial radius. In rich clusters, most of the baryonic mass is in the gas phase, and the ratio of mass in gas/stars varies by a factor of 2–4. The baryonic fractions vary by a factor of ≈3 from cluster to cluster and almost always exceed 0.09 h50−[3/2] and thus are in fundamental conflict with the assumption of Ω = 1 and the results of big bang nucleosynthesis. The derived Fe abundances are 0.2–0.45 solar, and the abundances of O and Si for low redshift systems are 0.6–1.0 solar. This distribution is consistent with an origin in pure type II supernova. The amount of light and energy produced by these supernovae is very large, indicating their importance in influencing the formation of clusters and galaxies. The lack of evolution of Fe to a redshift of z ≈ 0.4 argues for very early enrichment of the cluster gas. Groups show a wide range of abundances, 0.1–0.5 solar. The results of an x-ray survey indicate that the contribution of groups to the mass density of the universe is likely to be larger than 0.1 h50−2. Many of the very poor groups have large x-ray halos and are filled with small galaxies whose velocity dispersion is a good match to the x-ray temperatures.

Regulation of Epidermal Growth Factor Receptor Signaling by Endocytosis and Intracellular Trafficking

Ligand activation of the epidermal growth factor receptor (EGFR) leads to its rapid internalization and eventual delivery to lysosomes. This process is thought to be a mechanism to attenuate signaling, but signals could potentially be generated after endocytosis. To directly evaluate EGFR signaling during receptor trafficking, we developed a technique to rapidly and selectively isolate internalized EGFR and associated molecules with the use of reversibly biotinylated anti-EGFR antibodies. In addition, we developed antibodies specific to tyrosine-phosphorylated EGFR. With the use of a combination of fluorescence imaging and affinity precipitation approaches, we evaluated the state of EGFR activation and substrate association during trafficking in epithelial cells. We found that after internalization, EGFR remained active in the early endosomes. However, receptors were inactivated before degradation, apparently due to ligand removal from endosomes. Adapter molecules, such as Shc, were associated with EGFR both at the cell surface and within endosomes. Some molecules, such as Grb2, were primarily found associated with surface EGFR, whereas others, such as Eps8, were found only with intracellular receptors. During the inactivation phase, c-Cbl became EGFR associated, consistent with its postulated role in receptor attenuation. We conclude that the association of the EGFR with different proteins is compartment specific. In addition, ligand loss is the proximal cause of EGFR inactivation. Thus, regulated trafficking could potentially influence the pattern as well as the duration of signal transduction.

Self-standing curved crystals for X and Gamma rays focusing

The efficiency of a Laue lens for X and Gamma ray focusing in the energy range 60 ÷ 600 keV is closely linked to the diffraction efficiency of the single crystals composing the lens. A powerful focusing system is crucial for applications like medical imaging and X ray astronomy where wide beams must be focused. Mosaic crystals with a high density, such as Cu or Au, and bent crystals with curved diffracting planes (CDP) are considered for the realization of a focusing system for X rays, owing to their high diffraction efficiency. In this work, a comparison of the efficiency of CDP crystals and mosaic crystals was performed on the basis of the theory of X-ray diffraction. Si, GaAs and Ge CDP crystals with optimized thicknesses and moderate radii of curvature of several tens of metres demonstrate comparable or superior performance with respect to the higher atomic number mosaic crystals generally used. A simplified approach for calculating the integrated reflectivity of the crystals is applied. A bending technique used during this work to realize CDP crystals consists in a controlled surface damaging induced by a mechanical lapping process. A compressive strained layer of few micrometres in thickness is generated and causes the convex curvature of the damaged side of the crystal. Another new bending technique is developed and the main results are shown. The process consists on a film deposition of a selected bi-component epoxy resin on one side of crystal, made uniform in thickness by mean of a spin-coater. Choosing the speed of spin-coating, so changing the thickness of the film, a control of radius of curvature can be obtained. Moreover the possibility to combine the two bending technique to obtain CDP crystal with a stronger curvature in rather thick crystals was demonstrated. Detailed characterization of Si, and GaAs CDP crystals at low and high x-ray energies are performed on flat and bent crystals obtained with the damaging and the resin deposition technique. As expected an increase of diffraction efficiency in asymmetrical diffraction geometry in CDP crystals with respect to the flat ones is observed. On the other hand an unexpected increase of the integrated intensity in symmetrical geometry, not predicted by the theory, is observed in all the measurements performed with different set up. The experimental trend of the integrated reflectivity as a function of the radius of curvature is in a good agreement with that predicted by the theory of bent perfect crystals, so it is possible to conclude that the surface damage has a limited effect on the crystal reflectivity. A study of the integrated reflectivity in the energy range of interest (100÷350 keV) in CDP crystals realized with damaging and resin deposition technique at symmetrical and asymmetrical geometries was performed at ILL Institute. Also at these energies the diffraction efficiency of bent crystals was much larger (a 12 time increase is observed for bent crystals in asymmetrical 111 geometry) than that measured in flat crystals. The diffraction efficiency of CDP crystals realized with both techniques tends to coincide with that of flat crystals at very high energies (> 200 keV). This suggesting that also real flat perfect crystals can be considered as strongly bent or mosaic crystals at very high X ray energies.

Is ultrasound perfusion imaging capable of detecting mismatch? A proof-of-concept study in acute stroke patients.

In this study, we compared contrast-enhanced ultrasound perfusion imaging with magnetic resonance perfusion-weighted imaging or perfusion computed tomography for detecting normo-, hypo-, and nonperfused brain areas in acute middle cerebral artery stroke. We performed high mechanical index contrast-enhanced ultrasound perfusion imaging in 30 patients. Time-to-peak intensity of 10 ischemic regions of interests was compared to four standardized nonischemic regions of interests of the same patient. A time-to-peak >3 s (ultrasound perfusion imaging) or >4 s (perfusion computed tomography and magnetic resonance perfusion) defined hypoperfusion. In 16 patients, 98 of 160 ultrasound perfusion imaging regions of interests of the ischemic hemisphere were classified as normal, and 52 as hypoperfused or nonperfused. Ten regions of interests were excluded due to artifacts. There was a significant correlation of the ultrasound perfusion imaging and magnetic resonance perfusion or perfusion computed tomography (Pearson`s chi-squared test 79.119, p < 0.001) (OR 0.1065, 95% CI 0.06-0.18). No perfusion in ultrasound perfusion imaging (18 regions of interests) correlated highly with diffusion restriction on magnetic resonance imaging (Pearson's chi-squared test 42.307, p < 0.001). Analysis of receiver operating characteristics proved a high sensitivity of ultrasound perfusion imaging in the diagnosis of hypoperfused area under the curve, (AUC = 0.917; p < 0.001) and nonperfused (AUC = 0.830; p < 0.001) tissue in comparison with perfusion computed tomography and magnetic resonance perfusion. We present a proof of concept in determining normo-, hypo-, and nonperfused tissue in acute stroke by advanced contrast-enhanced ultrasound perfusion imaging.

Digital Classics Outside the Echo-Chamber : Teaching, Knowledge Exchange and Public Engagement /

The international perspectives on these issues are especially valuable in an increasingly connected, but still institutionally and administratively diverse world. The research addressed in several chapters in this volume includes issues around technical standards bodies like EpiDoc and the TEI, engaging with ways these standards are implemented, documented, taught, used in the process of transcribing and annotating texts, and used to generate publications and as the basis for advanced textual or corpus research. Other chapters focus on various aspects of philological research and content creation, including collaborative or community driven efforts, and the issues surrounding editorial oversight, curation, maintenance and sustainability of these resources. Research into the ancient languages and linguistics, in particular Greek, and the language teaching that is a staple of our discipline, are also discussed in several chapters, in particular for ways in which advanced research methods can lead into language technologies and vice versa and ways in which the skills around teaching can be used for public engagement, and vice versa. A common thread through much of the volume is the importance of open access publication or open source development and distribution of texts, materials, tools and standards, both because of the public good provided by such models (circulating materials often already paid for out of the public purse), and the ability to reach non-standard audiences, those who cannot access rich university libraries or afford expensive print volumes. Linked Open Data is another technology that results in wide and free distribution of structured information both within and outside academic circles, and several chapters present academic work that includes ontologies and RDF, either as a direct research output or as essential part of the communication and knowledge representation. Several chapters focus not on the literary and philological side of classics, but on the study of cultural heritage, archaeology, and the material supports on which original textual and artistic material are engraved or otherwise inscribed, addressing both the capture and analysis of artefacts in both 2D and 3D, the representation of data through archaeological standards, and the importance of sharing information and expertise between the several domains both within and without academia that study, record and conserve ancient objects. Almost without exception, the authors reflect on the issues of interdisciplinarity and collaboration, the relationship between their research practice and teaching and/or communication with a wider public, and the importance of the role of the academic researcher in contemporary society and in the context of cutting edge technologies. How research is communicated in a world of instant- access blogging and 140-character micromessaging, and how our expectations of the media affect not only how we publish but how we conduct our research, are questions about which all scholars need to be aware and self-critical.