The molecular signature of the stroma response in prostate cancer-induced osteoblastic bone metastasis highlights expansion of hematopoietic and prostate epithelial stem cell niches

The reciprocal interaction between cancer cells and the tissue-specific stroma is critical for primary and metastatic tumor growth progression. Prostate cancer cells colonize preferentially bone (osteotropism), where they alter the physiological balance between osteoblast-mediated bone formation and osteoclast-mediated bone resorption, and elicit prevalently an osteoblastic response (osteoinduction). The molecular cues provided by osteoblasts for the survival and growth of bone metastatic prostate cancer cells are largely unknown. We exploited the sufficient divergence between human and mouse RNA sequences together with redefinition of highly species-specific gene arrays by computer-aided and experimental exclusion of cross-hybridizing oligonucleotide probes. This strategy allowed the dissection of the stroma (mouse) from the cancer cell (human) transcriptome in bone metastasis xenograft models of human osteoinductive prostate cancer cells (VCaP and C4-2B). As a result, we generated the osteoblastic bone metastasis-associated stroma transcriptome (OB-BMST). Subtraction of genes shared by inflammation, wound healing and desmoplastic responses, and by the tissue type-independent stroma responses to a variety of non-osteotropic and osteotropic primary cancers generated a curated gene signature ("Core" OB-BMST) putatively representing the bone marrow/bone-specific stroma response to prostate cancer-induced, osteoblastic bone metastasis. The expression pattern of three representative Core OB-BMST genes (PTN, EPHA3 and FSCN1) seems to confirm the bone specificity of this response. A robust induction of genes involved in osteogenesis and angiogenesis dominates both the OB-BMST and Core OB-BMST. This translates in an amplification of hematopoietic and, remarkably, prostate epithelial stem cell niche components that may function as a self-reinforcing bone metastatic niche providing a growth support specific for osteoinductive prostate cancer cells. The induction of this combinatorial stem cell niche is a novel mechanism that may also explain cancer cell osteotropism and local interference with hematopoiesis (myelophthisis). Accordingly, these stem cell niche components may represent innovative therapeutic targets and/or serum biomarkers in osteoblastic bone metastasis.

Comparison of gadoteric acid and gadobutrol for detection as well as morphologic and dynamic characterization of lesions on breast dynamic contrast-enhanced magnetic resonance imaging

OBJECTIVE In contrast to conventional breast imaging techniques, one major diagnostic benefit of breast magnetic resonance imaging (MRI) is the simultaneous acquisition of morphologic and dynamic enhancement characteristics, which are based on angiogenesis and therefore provide insights into tumor pathophysiology. The aim of this investigation was to intraindividually compare 2 macrocyclic MRI contrast agents, with low risk for nephrogenic systemic fibrosis, in the morphologic and dynamic characterization of histologically verified mass breast lesions, analyzed by blinded human evaluation and a fully automatic computer-assisted diagnosis (CAD) technique. MATERIALS AND METHODS Institutional review board approval and patient informed consent were obtained. In this prospective, single-center study, 45 women with 51 histopathologically verified (41 malignant, 10 benign) mass lesions underwent 2 identical examinations at 1.5 T (mean time interval, 2.1 days) with 0.1-mmol kg doses of gadoteric acid and gadobutrol. All magnetic resonance images were visually evaluated by 2 experienced, blinded breast radiologists in consensus and by an automatic CAD system, whereas the morphologic and dynamic characterization as well as the final human classification of lesions were performed based on the categories of the Breast imaging reporting and data system MRI atlas. Lesions were also classified by defining their probability of malignancy (morpho-dynamic index; 0%-100%) by the CAD system. Imaging results were correlated with histopathology as gold standard. RESULTS The CAD system coded 49 of 51 lesions with gadoteric acid and gadobutrol (detection rate, 96.1%); initial signal increase was significantly higher for gadobutrol than for gadoteric acid for all and the malignant coded lesions (P < 0.05). Gadoteric acid resulted in more postinitial washout curves and fewer continuous increases of all and the malignant lesions compared with gadobutrol (CAD hot spot regions, P < 0.05). Morphologically, the margins of the malignancies were different between the 2 agents, whereas gadobutrol demonstrated more spiculated and fewer smooth margins (P < 0.05). Lesion classifications by the human observers and by the morpho-dynamic index compared with the histopathologic results did not significantly differ between gadoteric acid and gadobutrol. CONCLUSIONS Macrocyclic contrast media can be reliably used for breast dynamic contrast-enhanced MRI. However, gadoteric acid and gadobutrol differed in some dynamic and morphologic characterization of histologically verified breast lesions in an intraindividual, comparison. Besides the standardization of technical parameters and imaging evaluation of breast MRI, the standardization of the applied contrast medium seems to be important to receive best comparable MRI interpretation.

Postmortem quantitative 1.5-T MRI for the differentiation and characterization of serous fluids, blood, CSF, and putrefied CSF.

The purpose of the present study was to investigate whether serous fluids, blood, cerebrospinal fluid (CSF), and putrefied CSF can be characterized and differentiated in synthetically calculated magnetic resonance (MR) images based on their quantitative T 1, T 2, and proton density (PD) values. Images from 55 postmortem short axis cardiac and 31 axial brain 1.5-T MR examinations were quantified using a quantification sequence. Serous fluids, fluid blood, sedimented blood, blood clots, CSF, and putrefied CSF were analyzed for their mean T 1, T 2, and PD values. Body core temperature was measured during the MRI scans. The fluid-specific quantitative values were related to the body core temperature. Equations to correct for temperature differences were generated. In a 3D plot as well as in statistical analysis, the quantitative T 1, T 2 and PD values of serous fluids, fluid blood, sedimented blood, blood clots, CSF, and putrefied CSF could be well differentiated from each other. The quantitative T 1 and T 2 values were temperature-dependent. Correction of quantitative values to a temperature of 37 °C resulted in significantly better discrimination between all investigated fluid mediums. We conclude that postmortem 1.5-T MR quantification is feasible to discriminate between blood, serous fluids, CSF, and putrefied CSF. This finding provides a basis for the computer-aided diagnosis and detection of fluids and hemorrhages.

Stiffness, Strength, and Failure Modes of Implant-Supported Monolithic Lithium Disilicate Crowns: Influence of Titanium and Zirconia Abutments

PURPOSE The objective of this study was to evaluate stiffness, strength, and failure modes of monolithic crowns produced using computer-aided design/computer-assisted manufacture, which are connected to diverse titanium and zirconia abutments on an implant system with tapered, internal connections. MATERIALS AND METHODS Twenty monolithic lithium disilicate (LS2) crowns were constructed and loaded on bone level-type implants in a universal testing machine under quasistatic conditions according to DIN ISO 14801. Comparative analysis included a 2 × 2 format: prefabricated titanium abutments using proprietary bonding bases (group A) vs nonproprietary bonding bases (group B), and customized zirconia abutments using proprietary Straumann CARES (group C) vs nonproprietary Astra Atlantis (group D) material. Stiffness and strength were assessed and calculated statistically with the Wilcoxon rank sum test. Cross-sections of each tested group were inspected microscopically. RESULTS Loaded LS2 crowns, implants, and abutment screws in all tested specimens (groups A, B, C, and D) did not show any visible fractures. For an analysis of titanium abutments (groups A and B), stiffness and strength showed equally high stability. In contrast, proprietary and nonproprietary customized zirconia abutments exhibited statistically significant differences with a mean strength of 366 N (Astra) and 541 N (CARES) (P < .05); as well as a mean stiffness of 884 N/mm (Astra) and 1,751 N/mm (CARES) (P < .05), respectively. Microscopic cross-sections revealed cracks in all zirconia abutments (groups C and D) below the implant shoulder. CONCLUSION Depending on the abutment design, prefabricated titanium abutment and proprietary customized zirconia implant-abutment connections in conjunction with monolithic LS2 crowns had the best results in this laboratory investigation.

Artificial Neural Nets with Interaction of Afferents

The aim is to obtain computationally more powerful, neuro physiologically founded, artificial neurons and neural nets. Artificial Neural Nets (ANN) of the Perceptron type evolved from the original proposal by McCulloch an Pitts classical paper [1]. Essentially, they keep the computing structure of a linear machine followed by a non linear operation. The McCulloch-Pitts formal neuron (which was never considered by the author’s to be models of real neurons) consists of the simplest case of a linear computation of the inputs followed by a threshold. Networks of one layer cannot compute anylogical function of the inputs, but only those which are linearly separable. Thus, the simple exclusive OR (contrast detector) function of two inputs requires two layers of formal neurons

Dendritic-Like Reliable Computation in Artificial Neurons

Dendritic computation is a term that has been in neuro physiological research for a long time [1]. It is still controversial and far for been clarified within the concepts of both computation and neurophysiology [2], [3]. In any case, it hasnot been integrated neither in a formal computational scheme or structure, nor into formulations of artificial neural nets. Our objective here is to formulate a type of distributed computation that resembles dendritic trees, in such a way that it shows the advantages of neural network distributed computation, mostly the reliability that is shown under the existence of holes (scotomas) in the computing net, without ?blind spots?.

Seed image analysis and taxonomy of Diplotaxis DC. (Brassicaceae, Brassiceae)

The genus Diplotaxis, comprising 32 or 34 species, plus several additional infraspecific taxa, displays a considerable degree of heterogeneity in the morphology, molecular markers, chromosome numbers and geographical amplitude of the species. The taxonomic relationships within the genus Diplotaxis were investigated by phenetic characterisation of germplasm belonging to 27 taxa of the genus, because there is an increasing interest in Diplotaxis, since some of its species (D. tenuifolia, D. muralis) are gathered or cultivated for human consumption, whereas others are frequent arable weeds (D. erucoides) in many European vineyards. Using a computer-aided vision system, 33 morpho-colorimetric features of seeds were electronically measured. The data were used to implement a statistical classifier, which is able to discriminate the taxa within the genus Diplotaxis, in order to compare the resulting species grouping with the current infrageneric systematics of this genus. Despite the high heterogeneity of the samples, due to the great intra-population variability, the stepwise Linear Discriminant Analysis method, applied to distinguish the groups, was able to reach over 80% correct identification. The results obtained allowed us to confirm the current taxonomic position of most taxa and suggested the taxonomic position of others for reconsideration.

Implementación de algoritmos para la manipulación de curvas concoides en diseño geométrico

Este proyecto se enmarca dentro de la Computación Simbólica y de los fundamentos matemáticos del Diseño Geométrico Asistido por ordenador (CAGD). Se abordara uno de los problemas principales en el ámbito del CAGD y que es la manipulación de las Curvas Concoide. La importancia del avance en la manipulación de las curvas concoide radica en el papel fundamental que desempeñan en múltiples aplicaciones en la actualidad dentro de campos de diversa índole tales como la medicina, la óptica, el electromagnetismo, la construcción, etc. El objetivo principal de este proyecto es el diseño e implementación de algoritmos para el estudio, cálculo y manipulación de curvas concoides, utilizando técnicas propias del Calculo Simbólico. Esta implementación se ha programado utilizando el sistema de computación simbólica Maple. El proyecto consiste en dos partes bien diferenciadas, una parte teórica y otra más practica. La primera incluye la descripción geométrica y definición formal de curvas concoide, así como las ideas y propiedades básicas. De forma más precisa, se presenta un estudio matemático sobre el análisis de racionalidad de estas curvas, explicando los algoritmos que serán implementados en las segunda parte, y que constituye el objetivo principal de este proyecto. Para cerrar esta parte, se presenta una pequeña introducción al sistema y a la programación en Maple. Por otro lado, la segunda parte de este proyecto es totalmente original, y en ella el autor desarrolla las implementaciones en Maple de los algoritmos presentados en la parte anterior, así como la creación de un paquete Maple que las recoge. Por último, se crean las paginas de ayudas en el sistema Maple para la correcta utilización del paquete matemático anteriormente mencionado. Una vez terminada la parte de implementación, se aplican los algoritmos implementados a una colección de curvas clásicas conocidas, recogiendo los datos y resultados obtenidos en un atlas de curvas. Finalmente, se presenta una recopilación de las aplicaciones más destacadas en las que las concoides desempeñan un papel importante así como una breve reseña sobre las concoides de superficies, objeto de varios estudios en la actualidad y a los que se considera que el presente proyecto les puede resultar de gran utilidad. Abstract This project is set up in the framework of Symbolic Computation as well as in the implementation of algebraic-geometric problems that arise from Computer Aided Geometric Design (C.A.G.D.) applications. We address problems related to conchoid curves. The importance of these curves is the fundamental role that they play in current applications as medicine, optics, electromagnetism, construction, etc. The main goal of this project is to design and implement some algorithms to solve problems in studying, calculating and generating conchoid curves with symbolic computation techniques. For this purpose, we program our implementations in the symbolic system “Maple". The project consists of two differentiated parts, one more theoretical part and another part more practical. The first one includes the description of conchoid curves as well as the basic ideas about the concept and its basic properties. More precisely, we introduce in this part the mathematical analysis of the rationality of the conchoids, and we present the algorithms that will be implemented. Furthermore, the reader will be brie y introduced in Maple programming. On the other hand, the second part of this project is totally original. In this more practical part, the author presents the implemented algorithms and a Maple package that includes them, as well as their help pages. These implemented procedures will be check and illustrated with some classical and well known curves, collecting the main properties of the conchoid curves obtained in a brief atlas. Finally, a compilation of the most important applications where conchoids play a fundamental role, and a brief introduction to the conchoids of surfaces, subject of several studies today and where this project could be very useful, are presented.

Control and command systems concepts from early work on a Mars Rover

We recover and develop some robotic systems concepts (on the light of present systems tools) that were originated for an intended Mars Rover in the sixties of the last century at the Instrumentation Laboratory of MIT, where one of the authors was involved. The basic concepts came from the specifications for a type of generalized robot inspired in the structure of the vertebrate nervous systems, where the decision system was based in the structure and function of the Reticular Formation (RF). The vertebrate RF is supposed to commit the whole organism to one among various modes of behavior, so taking the decisions about the present overall task. That is, it is a kind of control and command system. In this concepts updating, the basic idea is that the RF comprises a set of computing units such that each computing module receives information only from a reduced part of the overall, little processed sensory inputs. Each computing unit is capable of both general diagnostics about overall input situations and of specialized diagnostics according to the values of a concrete subset of the input lines. Slave systems to this command and control computer, there are the sensors, the representations of external environment, structures for modeling and planning and finally, the effectors acting in the external world.

Conchoid surfaces of spheres

The conchoid of a surface F with respect to given xed point O is roughly speaking the surface obtained by increasing the radius function with respect to O by a constant. This paper studies conchoid surfaces of spheres and shows that these surfaces admit rational parameterizations. Explicit parameterizations of these surfaces are constructed using the relations to pencils of quadrics in R3 and R4. Moreover we point to remarkable geometric properties of these surfaces and their construction.

Modelos predictivos para el estudio del abandono en centros universitarios

El abandono universitario es un problema que siempre ha afectado a las distintas universidades públicas. La Universidad Politécnica de Madrid, en concreto la Escuela Técnica Superior de Ingenieros Informáticos, pretende reducir dicho abandono aplicando técnicas de Data Mining para detectar aquellos alumnos que abandonan antes de que lo hagan. Este proyecto, a través de la metodología CRISP-DM (CRoss Industry Standard Process for Data Mining) y con los datos obtenidos del SIIU (Sistema Integrado de Información Universitaria), tiene como fin identificar a los alumnos que abandonan el primer añoo para poder aplicar distintas políticas en ellos y así evitarlo. ---ABSTRACT---Early university abandonment is a problem which has affected different public universities. The Universidad Polit´ecnica de Madrid (Polytechnic University of Madrid), inparticular the Escuela Técnica Superior de Ingenieros Informáticos (Computer Science Engineering School), wants to reduce this abandonment rate using Data Mining techniques to find students who are likely to leave before they do. The purpose of this project, through CRISP-DM (CRoss Industry Standard Process for Data Mining) methodology and using the data from SIIU (Sistema Integrado de Informaci´on Universitaria), is to identify those students who leave the first year in order to apply different policies and avoid it.

Optimization methods for the operating room management under uncertainty: stochastic programming vs. decomposition approach

The operating theatres are the engine of the hospitals; proper management of the operating rooms and its staff represents a great challenge for managers and its results impact directly in the budget of the hospital. This work presents a MILP model for the efficient schedule of multiple surgeries in Operating Rooms (ORs) during a working day. This model considers multiple surgeons and ORs and different types of surgeries. Stochastic strategies are also implemented for taking into account the uncertain in surgery durations (pre-incision, incision, post-incision times). In addition, a heuristic-based methods and a MILP decomposition approach is proposed for solving large-scale ORs scheduling problems in computational efficient way. All these computer-aided strategies has been implemented in AIMMS, as an advanced modeling and optimization software, developing a user friendly solution tool for the operating room management under uncertainty.

Managing daily surgery schedules in a teaching hospital: a mixed-integer optimization approach

Background: This study examined the daily surgical scheduling problem in a teaching hospital. This problem relates to the use of multiple operating rooms and different types of surgeons in a typical surgical day with deterministic operation durations (preincision, incision, and postincision times). Teaching hospitals play a key role in the health-care system; however, existing models assume that the duration of surgery is independent of the surgeon's skills. This problem has not been properly addressed in other studies. We analyze the case of a Spanish public hospital, in which continuous pressures and budgeting reductions entail the more efficient use of resources. Methods: To obtain an optimal solution for this problem, we developed a mixed-integer programming model and user-friendly interface that facilitate the scheduling of planned operations for the following surgical day. We also implemented a simulation model to assist the evaluation of different dispatching policies for surgeries and surgeons. The typical aspects we took into account were the type of surgeon, potential overtime, idling time of surgeons, and the use of operating rooms. Results: It is necessary to consider the expertise of a given surgeon when formulating a schedule: such skill can decrease the probability of delays that could affect subsequent surgeries or cause cancellation of the final surgery. We obtained optimal solutions for a set of given instances, which we obtained through surgical information related to acceptable times collected from a Spanish public hospital. Conclusions: We developed a computer-aided framework with a user-friendly interface for use by a surgical manager that presents a 3-D simulation of the problem. Additionally, we obtained an efficient formulation for this complex problem. However, the spread of this kind of operation research in Spanish public health hospitals will take a long time since there is a lack of knowledge of the beneficial techniques and possibilities that operational research can offer for the health-care system.

Sistema multiplataforma de gestión integral de huertos urbanos

En este Proyecto Fin de Grado se construirá una herramienta de gestión integral de centros hortícolas donde una serie de huertos cuidados por personas en situación de discapacidad son alquilados a terceros. Esta iniciativa se lleva a cabo gracias a la iniciativa “La Huerta de Montecarmelo” de la Fundación Carmen Pardo-Valcarce de Madrid. Este proyecto es el resultado de la colaboración entre la Escuela Técnica Superior de Ingeniería de Sistemas Informáticos y la Fundación, a través de un programa de Prácticas Externas que duró doce meses. Por una parte, tras años de trabajo en esta Obra Social, se encontró que muchos de los clientes, pasado el verano, se desvinculaban de las tareas y del medio. A fin de solucionar esos problemas, se propuso construir una aplicación web, comunicada con otros dispositivos, como Smartphones, permitiendo un flujo de trabajo más ágil y notificando a los arrendatarios de cada cambio en sus huertos, por ejemplo: fotos recientes, notificaciones de recolecta o futuros cursos. El proyecto se llevó a cabo con éxito a lo largo de 2012 y 2013. Abstract In this Final Degree Project we build a complete horticulture center management tool where a set of gardens, which are kept by people with disabilities, are leased to third parties. This project is carried out within the La Huerta Montecarmelo initiative of the Carmen Pardo-Valcarce Foundation in Madrid. The project was the result of collaboration between the School of Computer Systems Engineering of the Technical University of Madrid and that Foundation through an External Practices program that lasted twelve months. By one hand, over the years of Social Work in this initiative, it was found that some clients after spring were easily disconnected from the tasks involved to the garden. By the other, all the management of more than two hundred of gardens becomes a very complex task due to lots of paperwork. To solve these problems and more, we proposed to build a web application, relying on other devices, such as Smartphones, allowing a more agile workflow and notifying customers of any change related to its garden, for example: recent photographs, notifications of harvest or future courses. The project was successfully carried out throughout 2012 and 2013.

Crowdsourcing without a crowd : Reliable online species identification using Bayesian models to minimize crowd size

Acknowledgment This research is supported by an award made by the RCUK Digital Economy program to the University of Aberdeen’s dot.rural Digital Economy Hub (ref. EP/G066051/1).