Time-lapse microscopy and classification of 2D human mesenchymal stem cells based on cell shape picks up myogenic from osteogenic and adipogenic differentiation

Current methods to characterize mesenchymal stem cells (MSCs) are limited to CD marker expression, plastic adherence and their ability to differentiate into adipogenic, osteogenic and chondrogenic precursors. It seems evident that stem cells undergoing differentiation should differ in many aspects, such as morphology and possibly also behaviour; however, such a correlation has not yet been exploited for fate prediction of MSCs. Primary human MSCs from bone marrow were expanded and pelleted to form high-density cultures and were then randomly divided into four groups to differentiate into adipogenic, osteogenic chondrogenic and myogenic progenitor cells. The cells were expanded as heterogeneous and tracked with time-lapse microscopy to record cell shape, using phase-contrast microscopy. The cells were segmented using a custom-made image-processing pipeline. Seven morphological features were extracted for each of the segmented cells. Statistical analysis was performed on the seven-dimensional feature vectors, using a tree-like classification method. Differentiation of cells was monitored with key marker genes and histology. Cells in differentiation media were expressing the key genes for each of the three pathways after 21 days, i.e. adipogenic, osteogenic and chondrogenic, which was also confirmed by histological staining. Time-lapse microscopy data were obtained and contained new evidence that two cell shape features, eccentricity and filopodia (= 'fingers') are highly informative to classify myogenic differentiation from all others. However, no robust classifiers could be identified for the other cell differentiation paths. The results suggest that non-invasive automated time-lapse microscopy could potentially be used to predict the stem cell fate of hMSCs for clinical application, based on morphology for earlier time-points. The classification is challenged by cell density, proliferation and possible unknown donor-specific factors, which affect the performance of morphology-based approaches. Copyright © 2012 John Wiley & Sons, Ltd.

Payone : incentive for epidemic protocol-based anonymity system

Anonymity systems maintain the anonymity of communicating nodes by camouflaging them, either with peer nodes generating dummy traffic or with peer nodes participating in the actual communication process. The probability of any adversary breaking down the anonymity of the communicating nodes is inversely proportional to the number of peer nodes participating in the network. Hence to maintain the anonymity of the communicating nodes, a large number of peer nodes are needed. Lack of peer availability weakens the anonymity of any large scale anonymity system. This work proposes PayOne, an incentive based scheme for promoting peer availability. PayOne aims to increase the peer availability by encouraging nodes to participate in the anonymity system by awarding them with incentives and thereby promoting the anonymity strength. Existing incentive schemes are designed for single path based approaches. There is no incentive scheme for multipath based or epidemic based anonymity systems. This work has been specifically designed for epidemic protocols and has been implemented over MuON, one of the latest entries to the area of multicasting based anonymity systems. MuON is a peer-to-peer based anonymity system which uses epidemic protocol for data dissemination. Existing incentive schemes involve paying every intermediate node that is involved in the communication between the initiator and the receiver. These schemes are not appropriate for epidemic based anonymity systems due to the incurred overhead. PayOne differs from the existing schemes because it involves paying a single intermediate node that participates in the network. The intermediate node can be any random node that participates in the communication and does not necessarily need to lie in the communication path between the initiator and the receiver. The light-weight characteristics of PayOne make it viable for large-scale epidemic based anonymity systems.

A comparison of pixel and object-based land cover classification. A case study of the Asmara region, Eritrea

In this paper we compare the performance of two image classification paradigms (object- and pixel-based) for creating a land cover map of Asmara, the capital of Eritrea and its surrounding areas using a Landsat ETM+ imagery acquired in January 2000. The image classification methods used were maximum likelihood for the pixel-based approach and Bhattacharyya distance for the object-oriented approach available in, respectively, ArcGIS and SPRING software packages. Advantages and limitations of both approaches are presented and discussed. Classifications outputs were assessed using overall accuracy and Kappa indices. Pixel- and object-based classification methods result in an overall accuracy of 78% and 85%, respectively. The Kappa coefficient for pixel- and object-based approaches was 0.74 and 0.82, respectively. Although pixel-based approach is the most commonly used method, assessment and visual interpretation of the results clearly reveal that the object-oriented approach has advantages for this specific case-study.

Invited Abstract: Issues with State-based Energy Consumption Modelling

Energy consumption modelling by state based approaches often assume constant energy consumption values in each state. However, it happens in certain situations that during state transitions or even during a state the energy consumption is not constant and does fluctuate. This paper discusses those issues by presenting some examples from wireless sensor and wireless local area networks for such cases and possible solutions.

An MILP-based heuristic for staff scheduling problems with acceptance levels

We present a real-world staff-assignment problem that was reported to us by a provider of an online workforce scheduling software. The problem consists of assigning employees to work shifts subject to a large variety of requirements related to work laws, work shift compatibility, workload balancing, and personal preferences of employees. A target value is given for each requirement, and all possible deviations from these values are associated with acceptance levels. The objective is to minimize the total number of deviations in ascending order of the acceptance levels. We present an exact lexicographic goal programming MILP formulation and an MILP-based heuristic. The heuristic consists of two phases: in the first phase a feasible schedule is built and in the second phase parts of the schedule are iteratively re-optimized by applying an exact MILP model. A major advantage of such MILP-based approaches is the flexibility to account for additional constraints or modified planning objectives, which is important as the requirements may vary depending on the company or planning period. The applicability of the heuristic is demonstrated for a test set derived from real-world data. Our computational results indicate that the heuristic is able to devise optimal solutions to non-trivial problem instances, and outperforms the exact lexicographic goal programming formulation on medium- and large-sized problem instances.

A novel organ-slice culturing system to simulate meniscal repair: Proof of concept using a synovium-based pool of meniscoprogenitor cells.

Meniscal injuries can occur secondary to trauma or be instigated by the changes in knee-joint function that are associated with aging, osteo- and rheumatoid arthritis, disturbances in gait and obesity. Sixty per cent of persons over 50 years of age manifest signs of meniscal pathology. The surgical and arthroscopic measures that are currently implemented to treat meniscal deficiencies bring only transient relief from pain and effect but a temporary improvement in joint function. Although tissue-engineering-based approaches to meniscal repair are now being pursued, an appropriate in-vitro model has not been conceived. The aim of this study was to develop an organ-slice culturing system to simulate the repair of human meniscal lesions in vitro. The model consists of a ring of bovine meniscus enclosing a chamber that represents the defect and reproduces its sequestered physiological microenvironment. The defect, which is closed with a porous membrane, is filled with fragments of synovial tissue, as a source of meniscoprogenitor cells, and a fibrin-embedded, calcium-phosphate-entrapped depot of the meniscogenic agents BMP-2 and TGF-ß1. After culturing for 2 to 6 weeks, the constructs were evaluated histochemically and histomorphometrically, as well as immunohistochemically for the apoptotic marker caspase 3 and collagen types I and II. Under the defined conditions, the fragments of synovium underwent differentiation into meniscal tissue, which bonded with the parent meniscal wall. Both the parent and the neoformed meniscal tissue survived the duration of the culturing period without significant cell losses. The concept on which the in-vitro system is based was thus validated. This article is protected by copyright. All rights reserved.

Differentiating the Multipoint Expected Improvement for Optimal Batch Design

This work deals with parallel optimization of expensive objective functions which are modelled as sample realizations of Gaussian processes. The study is formalized as a Bayesian optimization problem, or continuous multi-armed bandit problem, where a batch of q > 0 arms is pulled in parallel at each iteration. Several algorithms have been developed for choosing batches by trading off exploitation and exploration. As of today, the maximum Expected Improvement (EI) and Upper Confidence Bound (UCB) selection rules appear as the most prominent approaches for batch selection. Here, we build upon recent work on the multipoint Expected Improvement criterion, for which an analytic expansion relying on Tallis’ formula was recently established. The computational burden of this selection rule being still an issue in application, we derive a closed-form expression for the gradient of the multipoint Expected Improvement, which aims at facilitating its maximization using gradient-based ascent algorithms. Substantial computational savings are shown in application. In addition, our algorithms are tested numerically and compared to state-of-the-art UCB-based batchsequential algorithms. Combining starting designs relying on UCB with gradient-based EI local optimization finally appears as a sound option for batch design in distributed Gaussian Process optimization.

A practice-based culminating experience: Writing a HRSA grant application with Texas Organ Sharing Alliance for public education efforts to increase solid organ donation

In November 2010, nearly 110,000 people in the United States were waiting for organs for transplantation. Despite the fact that the organ donor registration rate has doubled in the last year, Texas has the lowest registration rate in the nation. Due to the need for improved registration rates in Texas, this practice-based culminating experience was to write an application for federal funding for the central Texas organ procurement organization, Texas Organ Sharing Alliance. The culminating experience has two levels of significance for public health – (1) to engage in an activity to promote organ donation registration, and (2) to provide professional experience in grant writing. ^ The process began with a literature review. The review was to identify successful intervention activities in motivating organ donation registration that could be used in intervention design for the grant application. Conclusions derived from the literature review included (1) the need to specifically encourage family discussions, (2) religious and community leaders can be leveraged to facilitate organ donation conversations in families, (3) communication content must be culturally sensitive and (4) ethnic disparities in transplantation must be acknowledged and discussed.^ Post the literature review; the experience followed a five step process of developing the grant application. The steps included securing permission to proceed, assembling a project team, creation of a project plan and timeline, writing each element of the grant application including the design of proposed intervention activities, and completion of the federal grant application. ^ After the grant application was written, an evaluation of the grant writing process was conducted. Opportunities for improvement were identified. The first opportunity was the need for better timeline management to allow for review of the application by an independent party, iterative development of the budget proposal, and development of collaborative partnerships. Another improvement opportunity was the management of conflict regarding the design of the intervention that stemmed from marketing versus evidence-based approaches. The most important improvement opportunity was the need to develop a more exhaustive evaluation plan.^ Eight supplementary files are attached to appendices: Feasibility Discussion in Appendix 1, Grant Guidance and Workshop Notes in Appendix 2, Presentation to Texas Organ Sharing Alliance in Appendix 3, Team Recruitment Presentation in Appendix 5, Grant Project Narrative in Appendix 7, Federal Application Form in Appendix 8, and Budget Workbook with Budget Narrative in Appendix 9.^

Model-based changes in global annual mean surface temperature change (Delta T_g) and radiative forcing due to land ice albedo changes (Delta R_[LI]) over the last 5 Myr, supplementary material

It is still an open question how equilibrium warming in response to increasing radiative forcing - the specific equilibrium climate sensitivity S - depends on background climate. We here present palaeodata-based evidence on the state dependency of S, by using CO2 proxy data together with a 3-D ice-sheet-model-based reconstruction of land ice albedo over the last 5 million years (Myr). We find that the land ice albedo forcing depends non-linearly on the background climate, while any non-linearity of CO2 radiative forcing depends on the CO2 data set used. This non-linearity has not, so far, been accounted for in similar approaches due to previously more simplistic approximations, in which land ice albedo radiative forcing was a linear function of sea level change. The latitudinal dependency of ice-sheet area changes is important for the non-linearity between land ice albedo and sea level. In our set-up, in which the radiative forcing of CO2 and of the land ice albedo (LI) is combined, we find a state dependence in the calculated specific equilibrium climate sensitivity, S[CO2,LI], for most of the Pleistocene (last 2.1 Myr). During Pleistocene intermediate glaciated climates and interglacial periods, S[CO2,LI] is on average ~ 45 % larger than during Pleistocene full glacial conditions. In the Pliocene part of our analysis (2.6-5 Myr BP) the CO2 data uncertainties prevent a well-supported calculation for S[CO2,LI], but our analysis suggests that during times without a large land ice area in the Northern Hemisphere (e.g. before 2.82 Myr BP), the specific equilibrium climate sensitivity, S[CO2,LI], was smaller than during interglacials of the Pleistocene. We thus find support for a previously proposed state change in the climate system with the widespread appearance of northern hemispheric ice sheets. This study points for the first time to a so far overlooked non-linearity in the land ice albedo radiative forcing, which is important for similar palaeodata-based approaches to calculate climate sensitivity. However, the implications of this study for a suggested warming under CO2 doubling are not yet entirely clear since the details of necessary corrections for other slow feedbacks are not fully known and the uncertainties that exist in the ice-sheet simulations and global temperature reconstructions are large.

High definition video quality assessment metric built upon full reference ratios

Métrica de calidad de video de alta definición construida a partir de ratios de referencia completa. La medida de calidad de video, en inglés Visual Quality Assessment (VQA), es uno de los mayores retos por solucionar en el entorno multimedia. La calidad de vídeo tiene un impacto altísimo en la percepción del usuario final (consumidor) de los servicios sustentados en la provisión de contenidos multimedia y, por tanto, factor clave en la valoración del nuevo paradigma denominado Calidad de la Experiencia, en inglés Quality of Experience (QoE). Los modelos de medida de calidad de vídeo se pueden agrupar en varias ramas según la base técnica que sustenta el sistema de medida, destacando en importancia los que emplean modelos psicovisuales orientados a reproducir las características del sistema visual humano, en inglés Human Visual System, del que toman sus siglas HVS, y los que, por el contrario, optan por una aproximación ingenieril en la que el cálculo de calidad está basado en la extracción de parámetros intrínsecos de la imagen y su comparación. A pesar de los avances recogidos en este campo en los últimos años, la investigación en métricas de calidad de vídeo, tanto en presencia de referencia (los modelos denominados de referencia completa), como en presencia de parte de ella (modelos de referencia reducida) e incluso los que trabajan en ausencia de la misma (denominados sin referencia), tiene un amplio camino de mejora y objetivos por alcanzar. Dentro de ellos, la medida de señales de alta definición, especialmente las utilizadas en las primeras etapas de la cadena de valor que son de muy alta calidad, son de especial interés por su influencia en la calidad final del servicio y no existen modelos fiables de medida en la actualidad. Esta tesis doctoral presenta un modelo de medida de calidad de referencia completa que hemos llamado PARMENIA (PArallel Ratios MEtric from iNtrInsic features Analysis), basado en la ponderación de cuatro ratios de calidad calculados a partir de características intrínsecas de la imagen. Son: El Ratio de Fidelidad, calculado mediante el gradiente morfológico o gradiente de Beucher. El Ratio de Similitud Visual, calculado mediante los puntos visualmente significativos de la imagen a través de filtrados locales de contraste. El Ratio de Nitidez, que procede de la extracción del estadístico de textura de Haralick contraste. El Ratio de Complejidad, obtenido de la definición de homogeneidad del conjunto de estadísticos de textura de Haralick PARMENIA presenta como novedad la utilización de la morfología matemática y estadísticos de Haralick como base de una métrica de medida de calidad, pues esas técnicas han estado tradicionalmente más ligadas a la teledetección y la segmentación de objetos. Además, la aproximación de la métrica como un conjunto ponderado de ratios es igualmente novedosa debido a que se alimenta de modelos de similitud estructural y otros más clásicos, basados en la perceptibilidad del error generado por la degradación de la señal asociada a la compresión. PARMENIA presenta resultados con una altísima correlación con las valoraciones MOS procedentes de las pruebas subjetivas a usuarios que se han realizado para la validación de la misma. El corpus de trabajo seleccionado procede de conjuntos de secuencias validados internacionalmente, de modo que los resultados aportados sean de la máxima calidad y el máximo rigor posible. La metodología de trabajo seguida ha consistido en la generación de un conjunto de secuencias de prueba de distintas calidades a través de la codificación con distintos escalones de cuantificación, la obtención de las valoraciones subjetivas de las mismas a través de pruebas subjetivas de calidad (basadas en la recomendación de la Unión Internacional de Telecomunicaciones BT.500), y la validación mediante el cálculo de la correlación de PARMENIA con estos valores subjetivos, cuantificada a través del coeficiente de correlación de Pearson. Una vez realizada la validación de los ratios y optimizada su influencia en la medida final y su alta correlación con la percepción, se ha realizado una segunda revisión sobre secuencias del hdtv test dataset 1 del Grupo de Expertos de Calidad de Vídeo (VQEG, Video Quality Expert Group) mostrando los resultados obtenidos sus claras ventajas. Abstract Visual Quality Assessment has been so far one of the most intriguing challenges on the media environment. Progressive evolution towards higher resolutions while increasing the quality needed (e.g. high definition and better image quality) aims to redefine models for quality measuring. Given the growing interest in multimedia services delivery, perceptual quality measurement has become a very active area of research. First, in this work, a classification of objective video quality metrics based on their underlying methodologies and approaches for measuring video quality has been introduced to sum up the state of the art. Then, this doctoral thesis describes an enhanced solution for full reference objective quality measurement based on mathematical morphology, texture features and visual similarity information that provides a normalized metric that we have called PARMENIA (PArallel Ratios MEtric from iNtrInsic features Analysis), with a high correlated MOS score. The PARMENIA metric is based on the pooling of different quality ratios that are obtained from three different approaches: Beucher’s gradient, local contrast filtering, and contrast and homogeneity Haralick’s texture features. The metric performance is excellent, and improves the current state of the art by providing a wide dynamic range that make easier to discriminate between very close quality coded sequences, especially for very high bit rates whose quality, currently, is transparent for quality metrics. PARMENIA introduces a degree of novelty against other working metrics: on the one hand, exploits the structural information variation to build the metric’s kernel, but complements the measure with texture information and a ratio of visual meaningful points that is closer to typical error sensitivity based approaches. We would like to point out that PARMENIA approach is the only metric built upon full reference ratios, and using mathematical morphology and texture features (typically used in segmentation) for quality assessment. On the other hand, it gets results with a wide dynamic range that allows measuring the quality of high definition sequences from bit rates of hundreds of Megabits (Mbps) down to typical distribution rates (5-6 Mbps), even streaming rates (1- 2 Mbps). Thus, a direct correlation between PARMENIA and MOS scores are easily constructed. PARMENIA may further enhance the number of available choices in objective quality measurement, especially for very high quality HD materials. All this results come from validation that has been achieved through internationally validated datasets on which subjective tests based on ITU-T BT.500 methodology have been carried out. Pearson correlation coefficient has been calculated to verify the accuracy of PARMENIA and its reliability.

Markov blanket-based approach for learning multi-dimensional Bayesian network classifiers: An application to predict the European Quality of Life-5 Dimensions (EQ-5D) from the 39-item Parkinson's Disease Questionnaire (PDQ-39)

Multi-dimensional Bayesian network classifiers (MBCs) are probabilistic graphical models recently proposed to deal with multi-dimensional classification problems, where each instance in the data set has to be assigned to more than one class variable. In this paper, we propose a Markov blanket-based approach for learning MBCs from data. Basically, it consists of determining the Markov blanket around each class variable using the HITON algorithm, then specifying the directionality over the MBC subgraphs. Our approach is applied to the prediction problem of the European Quality of Life-5 Dimensions (EQ-5D) from the 39-item Parkinson’s Disease Questionnaire (PDQ-39) in order to estimate the health-related quality of life of Parkinson’s patients. Fivefold cross-validation experiments were carried out on randomly generated synthetic data sets, Yeast data set, as well as on a real-world Parkinson’s disease data set containing 488 patients. The experimental study, including comparison with additional Bayesian network-based approaches, back propagation for multi-label learning, multi-label k-nearest neighbor, multinomial logistic regression, ordinary least squares, and censored least absolute deviations, shows encouraging results in terms of predictive accuracy as well as the identification of dependence relationships among class and feature variables.

RECLAMO: virtual and collaborative honeynets based on trust management and autonomous systems applied to intrusion management

Security intrusions in large systems is a problem due to its lack of scalability with the current IDS-based approaches. This paper describes the RECLAMO project, where an architecture for an Automated Intrusion Response System (AIRS) is being proposed. This system will infer the most appropriate response for a given attack, taking into account the attack type, context information, and the trust and reputation of the reporting IDSs. RECLAMO is proposing a novel approach: diverting the attack to a specific honeynet that has been dynamically built based on the attack information. Among all components forming the RECLAMO's architecture, this paper is mainly focused on defining a trust and reputation management model, essential to recognize if IDSs are exposing an honest behavior in order to accept their alerts as true. Experimental results confirm that our model helps to encourage or discourage the launch of the automatic reaction process.

Multi-Camera very wide baseline feature matching based on view-adaptive junction detection

This paper presents a strategy for solving the feature matching problem in calibrated very wide-baseline camera settings. In this kind of settings, perspective distortion, depth discontinuities and occlusion represent enormous challenges. The proposed strategy addresses them by using geometrical information, specifically by exploiting epipolar-constraints. As a result it provides a sparse number of reliable feature points for which 3D position is accurately recovered. Special features known as junctions are used for robust matching. In particular, a strategy for refinement of junction end-point matching is proposed which enhances usual junction-based approaches. This allows to compute cross-correlation between perfectly aligned plane patches in both images, thus yielding better matching results. Evaluation of experimental results proves the effectiveness of the proposed algorithm in very wide-baseline environments.

Agent-based modeling and simulation for the design of the future european Air Traffic Management system: the experience of CASSIOPEIA

The SESAR (Single European Sky ATM Research) program is an ambitious re-search and development initiative to design the future European air traffic man-agement (ATM) system. The study of the behavior of ATM systems using agent-based modeling and simulation tools can help the development of new methods to improve their performance. This paper presents an overview of existing agent-based approaches in air transportation (paying special attention to the challenges that exist for the design of future ATM systems) and, subsequently, describes a new agent-based approach that we proposed in the CASSIOPEIA project, which was developed according to the goals of the SESAR program. In our approach, we use agent models for different ATM stakeholders, and, in contrast to previous work, our solution models new collaborative decision processes for flow traffic management, it uses an intermediate level of abstraction (useful for simulations at larger scales), and was designed to be a practical tool (open and reusable) for the development of different ATM studies. It was successfully applied in three stud-ies related to the design of future ATM systems in Europe.

A gradient-enhanced large-deformation continuum damage model for fibre-reinforced materials

A non-local gradient-based damage formulation within a geometrically non-linear setting is presented. The hyperelastic constitutive response at local material point level is governed by a strain energy which is additively composed of an isotropic matrix and of an anisotropic fibre-reinforced material, respectively. The inelastic constitutive response is governed by a scalar [1–d]-type damage formulation, where only the anisotropic elastic part is assumed to be affected by the damage. Following the concept in Dimitrijević and Hackl [28], the local free energy function is enhanced by a gradient-term. This term essentially contains the gradient of the non-local damage variable which, itself, is introduced as an additional independent variable. In order to guarantee the equivalence between the local and non-local damage variable, a penalisation term is incorporated within the free energy function. Based on the principle of minimum total potential energy, a coupled system of Euler–Lagrange equations, i.e., the balance of linear momentum and the balance of the non-local damage field, is obtained and solved in weak form. The resulting coupled, highly non-linear system of equations is symmetric and can conveniently be solved by a standard incremental-iterative Newton–Raphson-type solution scheme. Several three-dimensional displacement- and force-driven boundary value problems—partially motivated by biomechanical application—highlight the mesh-objective characteristics and constitutive properties of the model and illustratively underline the capabilities of the formulation proposed