PHENOTHIAZINES INDUCE ABORTIVE AUTOPHAGY LEADING TO CANCER CELL DEATH

Autophagy is an evolutionarily conserved process that functions to maintain homeostasis and provides energy during nutrient deprivation and environmental stresses for the survival of cells by delivering cytoplasmic contents to the lysosomes for recycling and energy generation. Dysregulation of this process has been linked to human diseases including immune disorders, neurodegenerative muscular diseases and cancer. Autophagy is a double edged sword in that it has both pro-survival and pro-death roles in cancer cells. Its cancer suppressive roles include the clearance of damaged organelles, which could otherwise lead to inflammation and therefore promote tumorigenesis. In its pro-survival role, autophagy allows cancer cells to overcome cytotoxic stresses generated the cancer environment or cancer treatments such as chemotherapy and evade cell death. A better understanding of how drugs that perturb autophagy affect cancer cell signaling is of critical importance toimprove the cancer treatment arsenal. In order to gain insights in the relationship between autophagy and drug treatments, we conducted a high-throughput drug screen to identify autophagy modulators. Our high-throughput screen utilized image based fluorescent microscopy for single cell analysis to identify chemical perturbants of the autophagic process. Phenothiazines emerged as the largest family of drugs that alter the autophagic process by increasing LC3-II punctae levels in different cancer cell lines. In addition, we observed multiple biological effects in cancer cells treated with phenothiazines. Those antitumorigenic effects include decreased cell migration, cell viability, and ATP production along with abortive autophagy. Our studies highlight the potential role of phenothiazines as agents for combinational therapy with other chemotherapeutic agents in the treatment of different cancers.

Overall and local mechanical behaviour of dissimilar laser welded joints

The present investigation addresses the overall and local mechanical performance of dissimilar joints of low carbon steel (CS) and stainless steel (SS) thin sheets achieved by laser welding in case of heat source displacement from the weld gap centreline towards CS. Microstructure characterization and residua! strain scanning, carried out by neutron diffraction, were used to assess the joints features. It was found that the heat source position influences the base metals dilution and the residua! stress field associated to the welding process; the transverse residual stress is smaller than for the longitudinal component, of magnitudes close to the parent CS yield strength. Furthermore, compressive transverse residual stresses were encountered at the SS-weld interface. The tensile behavior of the joint different zones assessed by using a video-image based system (VIC-2D) reveals that the residual stress field, together with the positive difference in yield between the weld metal and the base materials protects the joint from being piastically deformed. The tensile loadings of flat transverse specimens generate the strain localization and failure in CS, far away from the weld.En este trabajo se exponen los resultados de una investigacion sobre el comportamiento mecanico de soldaduras disimiles acero inoxidable-acero al carbono, realizadas para unir chapas delgadas, desplazando la fuente de calor del eje longitudinal de la union soldada por laser sobre el acero al carbono. Se han determinado las caracteristicas microestructurales de la union soldada, las tensiones residuales generadas (mediante difraccion de neutrones) y las curvas tension-deformacion locales y globales, mediante medidas locales de deformacion empleando el sistema VIC-2D "video image correlation". El desplazamiento de la fuente de calor infiuye en la dilution de los metales base y el campo de tensiones residuales asociado al proceso de soldeo; las tensiones residuales medidas en direction longitudinal se aproximan al limite elastico del acero al carbono, mientras que las tensiones residuales transversales son menores, e incluso de compresion. El ensayo a traccion de la union soldada revela que las tensiones residuales y la diferencia de limite elastico entre los metales base y la soldadura propician que la rotura se produzca por inestabilidad plastica del acero al carbono, lejos de la soldadura, sin que la union plastifique.

Remote sensing of LAI, chlorophyll and leaf nitrogen pools of crop- and grasslands in five European landscapes.

Leaf nitrogen and leaf surface area influence the exchange of gases between terrestrial ecosystems and the atmosphere, and play a significant role in the global cycles of carbon, nitrogen and water. The purpose of this study is to use field-based and satellite remote-sensing-based methods to assess leaf nitrogen pools in five diverse European agricultural landscapes located in Denmark, Scotland (United Kingdom), Poland, the Netherlands and Italy. REGFLEC (REGularized canopy reFLECtance) is an advanced image-based inverse canopy radiative transfer modelling system which has shown proficiency for regional mapping of leaf area index (LAI) and leaf chlorophyll (CHLl) using remote sensing data. In this study, high spatial resolution (10–20 m) remote sensing images acquired from the multispectral sensors aboard the SPOT (Satellite For Observation of Earth) satellites were used to assess the capability of REGFLEC for mapping spatial variations in LAI, CHLland the relation to leaf nitrogen (Nl) data in five diverse European agricultural landscapes. REGFLEC is based on physical laws and includes an automatic model parameterization scheme which makes the tool independent of field data for model calibration. In this study, REGFLEC performance was evaluated using LAI measurements and non-destructive measurements (using a SPAD meter) of leaf-scale CHLl and Nl concentrations in 93 fields representing crop- and grasslands of the five landscapes. Furthermore, empirical relationships between field measurements (LAI, CHLl and Nl and five spectral vegetation indices (the Normalized Difference Vegetation Index, the Simple Ratio, the Enhanced Vegetation Index-2, the Green Normalized Difference Vegetation Index, and the green chlorophyll index) were used to assess field data coherence and to serve as a comparison basis for assessing REGFLEC model performance. The field measurements showed strong vertical CHLl gradient profiles in 26% of fields which affected REGFLEC performance as well as the relationships between spectral vegetation indices (SVIs) and field measurements. When the range of surface types increased, the REGFLEC results were in better agreement with field data than the empirical SVI regression models. Selecting only homogeneous canopies with uniform CHLl distributions as reference data for evaluation, REGFLEC was able to explain 69% of LAI observations (rmse = 0.76), 46% of measured canopy chlorophyll contents (rmse = 719 mg m−2) and 51% of measured canopy nitrogen contents (rmse = 2.7 g m−2). Better results were obtained for individual landscapes, except for Italy, where REGFLEC performed poorly due to a lack of dense vegetation canopies at the time of satellite recording. Presence of vegetation is needed to parameterize the REGFLEC model. Combining REGFLEC- and SVI-based model results to minimize errors for a "snap-shot" assessment of total leaf nitrogen pools in the five landscapes, results varied from 0.6 to 4.0 t km−2. Differences in leaf nitrogen pools between landscapes are attributed to seasonal variations, extents of agricultural area, species variations, and spatial variations in nutrient availability. In order to facilitate a substantial assessment of variations in Nl pools and their relation to landscape based nitrogen and carbon cycling processes, time series of satellite data are needed. The upcoming Sentinel-2 satellite mission will provide new multiple narrowband data opportunities at high spatio-temporal resolution which are expected to further improve remote sensing capabilities for mapping LAI, CHLl and Nl.

Automated processing of zebrafish imaging data: a survey

Due to the relative transparency of its embryos and larvae, the zebrafish is an ideal model organism for bioimaging approaches in vertebrates. Novel microscope technologies allow the imaging of developmental processes in unprecedented detail, and they enable the use of complex image-based read-outs for high-throughput/high-content screening. Such applications can easily generate Terabytes of image data, the handling and analysis of which becomes a major bottleneck in extracting the targeted information. Here, we describe the current state of the art in computational image analysis in the zebrafish system. We discuss the challenges encountered when handling high-content image data, especially with regard to data quality, annotation, and storage. We survey methods for preprocessing image data for further analysis, and describe selected examples of automated image analysis, including the tracking of cells during embryogenesis, heartbeat detection, identification of dead embryos, recognition of tissues and anatomical landmarks, and quantification of behavioral patterns of adult fish. We review recent examples for applications using such methods, such as the comprehensive analysis of cell lineages during early development, the generation of a three-dimensional brain atlas of zebrafish larvae, and high-throughput drug screens based on movement patterns. Finally, we identify future challenges for the zebrafish image analysis community, notably those concerning the compatibility of algorithms and data formats for the assembly of modular analysis pipelines.

Mechanical behavior and residual stress field of dissimilar laser welded joints

The present investigation addresses the mechanical behavior and residual stress field of dissimilar joints produced by laser welding. Microstructure characterization and residual strain scanning, carried out by neutron diffraction, were used to assess the joints features. It was found that the heat source position influences the base metals dilution and the residual stress field associated to the welding process. The tensile behavior of the joint, different zones achieved by using a video-image based system (VIC-2D) reveals that the residual stress field, together with the positive difference in yield between the weld metal and the base materials protects the joint from being plastically deformed.

Overall vs. local mechanical behaviour of ferritic austenitic steel joints made by laser welding

The present investigation addresses the overall and local mechanical performance of dissimilar joints of low carbon steel (CS) and stainless Steel (SS) thin sheets achieved by laser welding in case of heat source displacement from the weld gap centreline towards CS. Welding was performed on a Nd:YAG laser DY033 (3300 W) in a continuos wave (CW), keyhole mode. The tensile behavior of the joint different zones assessed by using a video-image based system (VIC-2D) reveals that the residual stress field, together with the positive difference in yield between the weld metal and the base materials protects the joint from being plastically deformed. The tensile loadings of flat transverse specimens generate the strain localization and failure in CS, far away from the weld.

Nuevo algoritmo de compresión multimedia: codificación por saltos logaritmicos

Quizás el Código Morse, inventado en 1838 para su uso en la telegrafía, es uno de los primeros ejemplos de la utilización práctica de la compresión de datos [1], donde las letras más comunes del alfabeto son codificadas con códigos más cortos que las demás. A partir de 1940 y tras el desarrollo de la teoría de la información y la creación de los primeros ordenadores, la compresión de la información ha sido un reto constante y fundamental entre los campos de trabajo de investigadores de todo tipo. Cuanto mayor es nuestra comprensión sobre el significado de la información, mayor es nuestro éxito comprimiéndola. En el caso de la información multimedia, su naturaleza permite la compresión con pérdidas, alcanzando así cotas de compresión imposibles para los algoritmos sin pérdidas. Estos “recientes” algoritmos con pérdidas han estado mayoritariamente basados en transformación de la información al dominio de la frecuencia y en la eliminación de parte de la información en dicho dominio. Transformar al dominio de la frecuencia posee ventajas pero también involucra unos costes computacionales inevitables. Esta tesis presenta un nuevo algoritmo de compresión multimedia llamado “LHE” (Logarithmical Hopping Encoding) que no requiere transformación al dominio de la frecuencia, sino que trabaja en el dominio del espacio. Esto lo convierte en un algoritmo lineal de reducida complejidad computacional. Los resultados del algoritmo son prometedores, superando al estándar JPEG en calidad y velocidad. Para ello el algoritmo utiliza como base la respuesta fisiológica del ojo humano ante el estímulo luminoso. El ojo, al igual que el resto de los sentidos, responde al logaritmo de la señal de acuerdo a la ley de Weber. El algoritmo se compone de varias etapas. Una de ellas es la medición de la “Relevancia Perceptual”, una nueva métrica que nos va a permitir medir la relevancia que tiene la información en la mente del sujeto y en base a la misma, degradar en mayor o menor medida su contenido, a través de lo que he llamado “sub-muestreado elástico”. La etapa de sub-muestreado elástico constituye una nueva técnica sin precedentes en el tratamiento digital de imágenes. Permite tomar más o menos muestras en diferentes áreas de una imagen en función de su relevancia perceptual. En esta tesis se dan los primeros pasos para la elaboración de lo que puede llegar a ser un nuevo formato estándar de compresión multimedia (imagen, video y audio) libre de patentes y de alto rendimiento tanto en velocidad como en calidad. ABSTRACT The Morse code, invented in 1838 for use in telegraphy, is one of the first examples of the practical use of data compression [1], where the most common letters of the alphabet are coded shorter than the rest of codes. From 1940 and after the development of the theory of information and the creation of the first computers, compression of information has been a constant and fundamental challenge among any type of researchers. The greater our understanding of the meaning of information, the greater our success at compressing. In the case of multimedia information, its nature allows lossy compression, reaching impossible compression rates compared with lossless algorithms. These "recent" lossy algorithms have been mainly based on information transformation to frequency domain and elimination of some of the information in that domain. Transforming the frequency domain has advantages but also involves inevitable computational costs. This thesis introduces a new multimedia compression algorithm called "LHE" (logarithmical Hopping Encoding) that does not require transformation to frequency domain, but works in the space domain. This feature makes LHE a linear algorithm of reduced computational complexity. The results of the algorithm are promising, outperforming the JPEG standard in quality and speed. The basis of the algorithm is the physiological response of the human eye to the light stimulus. The eye, like other senses, responds to the logarithm of the signal according with Weber law. The algorithm consists of several stages. One is the measurement of "perceptual relevance," a new metric that will allow us to measure the relevance of information in the subject's mind and based on it; degrade accordingly their contents, through what I have called "elastic downsampling". Elastic downsampling stage is an unprecedented new technique in digital image processing. It lets take more or less samples in different areas of an image based on their perceptual relevance. This thesis introduces the first steps for the development of what may become a new standard multimedia compression format (image, video and audio) free of patents and high performance in both speed and quality.

Ancient colour vision: Multiple opsin genes in the ancestral vertebrates

Molecular investigation of the origin of colour vision has discovered five visual pigment (opsin) genes, all of which are expressed in an agnathan (jawless) fish, the lamprey Geotria australis. Lampreys are extant representatives of an ancient group of vertebrates whose origins are thought to date back to at least the early Cambrian, approximately 540 million years ago [1.]. Phylogenetic analysis has identified the visual pigment opsin genes of G. australis as orthologues of the major classes of vertebrate opsin genes. Therefore, multiple opsin genes must have originated very early in vertebrate evolution, prior to the separation of the jawed and jawless vertebrate lineages, and thereby provided the genetic basis for colour vision in all vertebrate species. The southern hemisphere lamprey Geotria australis (Figure 1A,B) possesses a predominantly cone-based visual system designed for photopic (bright light) vision [2. S.P. Collin, I.C. Potter and C.R. Braekevelt, The ocular morphology of the southern hemisphere lamprey Geotria australis Gray, with special reference to optical specializations and the characterisation and phylogeny of photoreceptor types. Brain Behav. Evol. 54 (1999), pp. 96–111.2. and 3.]. Previous work identified multiple cone types suggesting that the potential for colour vision may have been present in the earliest members of this group. In order to trace the molecular evolution and origins of vertebrate colour vision, we have examined the genetic complement of visual pigment opsins in G. australis.

The temporal and spatial limits of compensation for fixational eye movements

High-fidelity eye tracking is combined with a perceptual grouping task to provide insight into the likely mechanisms underlying the compensation of retinal image motion caused by movement of the eyes. The experiments describe the covert detection of minute temporal and spatial offsets incorporated into a test stimulus. Analysis of eye motion on individual trials indicates that the temporal offset sensitivity is actually due to motion of the eye inducing artificial spatial offsets in the briefly presented stimuli. The results have strong implications for two popular models of compensation for fixational eye movements, namely efference copy and image-based models. If an efference copy model is assumed, the results place constraints on the spatial accuracy and source of compensation. If an image-based model is assumed then limitations are placed on the integration time window over which motion estimates are calculated. (c) 2006 Elsevier Ltd. All rights reserved.

A combined spectrophotometric and morphometric study of the lunar mare dome fields near Cauchy, Arago, Hortensius, and Milichius

In this Study we examine the spectral and morphometric properties of the four important lunar mare dome fields near Cauchy, Arago, Hortensius. and Milichius. We utilize Clementine UV vis mulfispectral data to examine the soil composition of the mare domes while employing telescopic CCD imagery to compute digital elevation maps in order to determine their morphometric properties, especially flank slope, height, and edifice Volume. After reviewing previous attempts to determine topographic data for lunar domes, we propose an image-based 3D reconstruction approach which is based on a combination of photoclinometry and shape from shading. Accordingly, we devise a classification scheme for lunar Marc domes which is based on a principal component analysis of the determined spectral and morphometric features. For the effusive mare domes of the examined fields we establish four Classes, two of which are further divided into two subclasses, respectively, where each class represents distinct combinations of spectral and morphometric dome properties. As a general trend, shallow and steep domes formed out of low-TiO2 basalts are observed in the Hortensius and Milichius dome fields, while the domes near Cauchy and Arago that consist of high-TiO2 basalts are all very shallow. The intrusive domes of our data set cover a wide continuous range of spectral and morphometric quantities, generally characterized by larger diameters and shallower flank slopes than effusive domes. A comparison to effusive and intrusive mare domes in other lunar regions, highland domes, and lunar cones has shown that the examined four mare dome fields display Such a richness in spectral properties and 3D dome shape that the established representation remains valid in a more global context. Furthermore, we estimate the physical parameters of dome formation for the examined domes based on a rheologic model. Each class of effusive domes defined in terms of spectral and morphometric properties is characterized by its specific range of values for lava viscosity, effusion rate, and duration of the effusion process. For our data set we report lava viscosities between about 10(2) and 10(8) Pas, effusion rates between 25 and 600 m(3) s(-1), and durations of the effusion process between three weeks and 18 years. Lava viscosity decreases with increasing R-415/R-750 spectral ratio and thus TiO2 content; however, the correlation is not strong, implying an important influence of further parameters like effusion temperature on lava viscosity.

Canonical solution groups of a homomorphism : manipulator kinematics, nonparametric regression and distributed object systems

The kinematic mapping of a rigid open-link manipulator is a homomorphism between Lie groups. The homomorphisrn has solution groups that act on an inverse kinematic solution element. A canonical representation of solution group operators that act on a solution element of three and seven degree-of-freedom (do!) dextrous manipulators is determined by geometric analysis. Seven canonical solution groups are determined for the seven do! Robotics Research K-1207 and Hollerbach arms. The solution element of a dextrous manipulator is a collection of trivial fibre bundles with solution fibres homotopic to the Torus. If fibre solutions are parameterised by a scalar, a direct inverse funct.ion that maps the scalar and Cartesian base space coordinates to solution element fibre coordinates may be defined. A direct inverse pararneterisation of a solution element may be approximated by a local linear map generated by an inverse augmented Jacobian correction of a linear interpolation. The action of canonical solution group operators on a local linear approximation of the solution element of inverse kinematics of dextrous manipulators generates cyclical solutions. The solution representation is proposed as a model of inverse kinematic transformations in primate nervous systems. Simultaneous calibration of a composition of stereo-camera and manipulator kinematic models is under-determined by equi-output parameter groups in the composition of stereo-camera and Denavit Hartenberg (DH) rnodels. An error measure for simultaneous calibration of a composition of models is derived and parameter subsets with no equi-output groups are determined by numerical experiments to simultaneously calibrate the composition of homogeneous or pan-tilt stereo-camera with DH models. For acceleration of exact Newton second-order re-calibration of DH parameters after a sequential calibration of stereo-camera and DH parameters, an optimal numerical evaluation of DH matrix first order and second order error derivatives with respect to a re-calibration error function is derived, implemented and tested. A distributed object environment for point and click image-based tele-command of manipulators and stereo-cameras is specified and implemented that supports rapid prototyping of numerical experiments in distributed system control. The environment is validated by a hierarchical k-fold cross validated calibration to Cartesian space of a radial basis function regression correction of an affine stereo model. Basic design and performance requirements are defined for scalable virtual micro-kernels that broker inter-Java-virtual-machine remote method invocations between components of secure manageable fault-tolerant open distributed agile Total Quality Managed ISO 9000+ conformant Just in Time manufacturing systems.

Introduction: the media, animal conservation and environmental education

Natural History filmmaking has a long history but the generic boundaries between it and environmental and conservation filmmaking are blurred. Nature, environment and animal imagery has been a mainstay of television, campaigning organisations and conservation bodies from Greenpeace to the Sierra Club, with vibrant images being used effectively on posters, leaflets and postcards, and in coffee table books, media releases, short films and viral emails to educate and inform the general public. However, critics suggest that wildlife film and photography frequently convey a false image of the state of the world’s flora and fauna. The environmental educator David Orr once remarked that all education is environmental education, and it is possible to see all image-based communication in the same way. The Media, Animal Conservation and Environmental Education has contributions from filmmakers, photographers, researchers and academics from across the globe. It explores the various ways in which film, television and video are, and can be, used by conservationists and educators to encourage both a greater awareness of environmental and conservation issues, and practical action designed to help endangered species. This book is based on a special issue of the journal Environmental Education Research.

The media, animal conservation and environmental education

Natural History filmmaking has a long history but the generic boundaries between it and environmental and conservation filmmaking are blurred. Nature, environment and animal imagery has been a mainstay of television, campaigning organisations and conservation bodies from Greenpeace to the Sierra Club, with vibrant images being used effectively on posters, leaflets and postcards, and in coffee table books, media releases, short films and viral emails to educate and inform the general public. However, critics suggest that wildlife film and photography frequently convey a false image of the state of the world’s flora and fauna. The environmental educator David Orr once remarked that all education is environmental education, and it is possible to see all image-based communication in the same way. The Media, Animal Conservation and Environmental Education has contributions from filmmakers, photographers, researchers and academics from across the globe. It explores the various ways in which film, television and video are, and can be, used by conservationists and educators to encourage both a greater awareness of environmental and conservation issues, and practical action designed to help endangered species. This book is based on a special issue of the journal Environmental Education Research.

Critical practice and the public pedagogy of environmental and conservation media

Natural History filmmaking has a long history but the generic boundaries between it and environmental and conservation filmmaking are blurred. Nature, environment and animal imagery has been a mainstay of television, campaigning organisations and conservation bodies from Greenpeace to the Sierra Club, with vibrant images being used effectively on posters, leaflets and postcards, and in coffee table books, media releases, short films and viral emails to educate and inform the general public. However, critics suggest that wildlife film and photography frequently convey a false image of the state of the world’s flora and fauna. The environmental educator David Orr once remarked that all education is environmental education, and it is possible to see all image-based communication in the same way. The Media, Animal Conservation and Environmental Education has contributions from filmmakers, photographers, researchers and academics from across the globe. It explores the various ways in which film, television and video are, and can be, used by conservationists and educators to encourage both a greater awareness of environmental and conservation issues, and practical action designed to help endangered species. This book is based on a special issue of the journal Environmental Education Research.

Studying green spectacular environmentalisms group

Natural History filmmaking has a long history but the generic boundaries between it and environmental and conservation filmmaking are blurred. Nature, environment and animal imagery has been a mainstay of television, campaigning organisations and conservation bodies from Greenpeace to the Sierra Club, with vibrant images being used effectively on posters, leaflets and postcards, and in coffee table books, media releases, short films and viral emails to educate and inform the general public. However, critics suggest that wildlife film and photography frequently convey a false image of the state of the world’s flora and fauna. The environmental educator David Orr once remarked that all education is environmental education, and it is possible to see all image-based communication in the same way. The Media, Animal Conservation and Environmental Education has contributions from filmmakers, photographers, researchers and academics from across the globe. It explores the various ways in which film, television and video are, and can be, used by conservationists and educators to encourage both a greater awareness of environmental and conservation issues, and practical action designed to help endangered species. This book is based on a special issue of the journal Environmental Education Research.