Molecular mechanism of the relaxin signaling pathways: Activation of cAMP, PI3K, and PKCzeta

Relaxin is a polypeptide hormone that has diverse effects on reproductive and non-reproductive tissues. Relaxin activates the G-protein coupled receptors, LGR7 and LRG8. Early studies described increased cAMP and protein kinase A activity upon relaxin treatment, but cAMP accumulation alone could not account for all of the relaxin-mediated effects. We utilized the human monocyte cell line THP-1 to study the mechanism of relaxin-stimulated CAMP production. ^ Relaxin treatment in THP-1 cells produces a biphasic time course in cAMP accumulation, where the first peak appears as early as 1–2 minutes with a second peak at 10–20 minutes. Selective inhibitors for phosphoinositide 3-kinase (P13K), such as wortmannin and LY294002, show a dose-dependent inhibition of relaxin-stimulated cAMP accumulation, specific for the second peak of the relaxin time course. Neither the effects of relaxin nor the inhibition of relaxin by LY294002 is mediated by the activity of phosphodiesterases. Furthermore, LY294002 blocks upregulation of vascular endothelial growth factor transcript levels by relaxin. ^ To further delineate relaxin signaling pathways, we searched for downstream targets of PI3K that could activate adenylyl cyclase (AC). Protein kinase C ζ (PKCζ) was a prime candidate because it activates types II and V AC. Chelerythrine chloride (a general PKC inhibitor) inhibits relaxin-induced cAMP production to the same degree as LY294002 (∼40%). Relaxin stimulates PKCζ translocation to the plasma membrane in THP-1, MCF-7, PHM1-31, and MMC cells, as shown by immunocytochemistry. PKCζ translocation is P13K-dependent and independent of cAMP production. Antisense PKCζ oligodeoxynucleotides (PKCζ-ODNs) deplete both PKCζ transcript and protein levels in THP-1 cells. PKCζ-ODNs abolish relaxin-mediated PKCζ translocation and inhibit relaxin stimulation of cAMP by 40%, as compared to mock and random ODN controls. Treatment with LY294002 in the presence of PKCζ-ODNs results in little further inhibition. Taken together, we present a novel role for PI3K and PKCζ in relaxin stimulation of cAMP and provide the first example of the PKCζ regulation of AC in an endogenous system. Furthermore, we have identified higher order complexes of AC isoforms and PKA anchoring proteins in attempts to explain the differential coupling of relaxin to cAMP and PI3K-signaling pathways in various cell types. ^

Biochar and Managed Perennial Ecosystems

Biochar is a carbon-rich material that is similar to charcoal. It is produced when biomass is burned in the absence of oxygen, a process otherwise known as pyrolysis. Pyrolysis and the production of biochar are currently being promoted as a means to both produce domestic fuel (bio-oil) while concurrently producing a co-product that increases crop yield and sequesters carbon in the soil (biochar). While there may be many potential benefits in the application of biochar to agricultural soils, such as enhanced soil fertility and improved soil water status, there are no studies of higher-order ecological and ecosystem effects of biochar and its potential synergistic interactions (either positive or negative) on complex perennial systems. The goal of this field experiment is to determine how biochar and manure addition directly affect ecosystem structure and function in perennial systems, specifically soil nutrients, water, plants, and soil organisms.

Lagrangian back-tracing results for Kohnen station; output of time dependent numerical experiment with a 3D nested Antarctic ice sheet model

A nested ice flow model was developed for eastern Dronning Maud Land to assist with the dating and interpretation of the EDML deep ice core. The model consists of a high-resolution higher-order ice dynamic flow model that was nested into a comprehensive 3-D thermomechanical model of the whole Antarctic ice sheet. As the drill site is on a flank position the calculations specifically take into account the effects of horizontal advection as deeper ice in the core originated from higher inland. First the regional velocity field and ice sheet geometry is obtained from a forward experiment over the last 8 glacial cycles. The result is subsequently employed in a Lagrangian backtracing algorithm to provide particle paths back to their time and place of deposition. The procedure directly yields the depth-age distribution, surface conditions at particle origin, and a suite of relevant parameters such as initial annual layer thickness. This paper discusses the method and the main results of the experiment, including the ice core chronology, the non-climatic corrections needed to extract the climatic part of the signal, and the thinning function. The focus is on the upper 89% of the ice core (appr. 170 kyears) as the dating below that is increasingly less robust owing to the unknown value of the geothermal heat flux. It is found that the temperature biases resulting from variations of surface elevation are up to half of the magnitude of the climatic changes themselves.

Interface discontinuity factors in the modal eigenspace of the multigroup diffusion matrix

Interface discontinuity factors based on the Generalized Equivalence Theory are commonly used in nodal homogenized diffusion calculations so that diffusion average values approximate heterogeneous higher order solutions. In this paper, an additional form of interface correction factors is presented in the frame of the Analytic Coarse Mesh Finite Difference Method (ACMFD), based on a correction of the modal fluxes instead of the physical fluxes. In the ACMFD formulation, implemented in COBAYA3 code, the coupled multigroup diffusion equations inside a homogenized region are reduced to a set of uncoupled modal equations through diagonalization of the multigroup diffusion matrix. Then, physical fluxes are transformed into modal fluxes in the eigenspace of the diffusion matrix. It is possible to introduce interface flux discontinuity jumps as the difference of heterogeneous and homogeneous modal fluxes instead of introducing interface discontinuity factors as the ratio of heterogeneous and homogeneous physical fluxes. The formulation in the modal space has been implemented in COBAYA3 code and assessed by comparison with solutions using classical interface discontinuity factors in the physical space

Uniformly Reweighted Belief Propagation: A Factor Graph Approach

Tree-reweighted belief propagation is a message passing method that has certain advantages compared to traditional belief propagation (BP). However, it fails to outperform BP in a consistent manner, does not lend itself well to distributed implementation, and has not been applied to distributions with higher-order interactions. We propose a method called uniformly-reweighted belief propagation that mitigates these drawbacks. After having shown in previous works that this method can substantially outperform BP in distributed inference with pairwise interaction models, in this paper we extend it to higher-order interactions and apply it to LDPC decoding, leading performance gains over BP.

Relational and Allegorical Semantics for Constraint Logic Programming

El cálculo de relaciones binarias fue creado por De Morgan en 1860 para ser posteriormente desarrollado en gran medida por Peirce y Schröder. Tarski, Givant, Freyd y Scedrov demostraron que las álgebras relacionales son capaces de formalizar la lógica de primer orden, la lógica de orden superior así como la teoría de conjuntos. A partir de los resultados matemáticos de Tarski y Freyd, esta tesis desarrolla semánticas denotacionales y operacionales para la programación lógica con restricciones usando el álgebra relacional como base. La idea principal es la utilización del concepto de semántica ejecutable, semánticas cuya característica principal es el que la ejecución es posible utilizando el razonamiento estándar del universo semántico, este caso, razonamiento ecuacional. En el caso de este trabajo, se muestra que las álgebras relacionales distributivas con un operador de punto fijo capturan toda la teoría y metateoría estándar de la programación lógica con restricciones incluyendo los árboles utilizados en la búsqueda de demostraciones. La mayor parte de técnicas de optimización de programas, evaluación parcial e interpretación abstracta pueden ser llevadas a cabo utilizando las semánticas aquí presentadas. La demostración de la corrección de la implementación resulta extremadamente sencilla. En la primera parte de la tesis, un programa lógico con restricciones es traducido a un conjunto de términos relacionales. La interpretación estándar en la teoría de conjuntos de dichas relaciones coincide con la semántica estándar para CLP. Las consultas contra el programa traducido son llevadas a cabo mediante la reescritura de relaciones. Para concluir la primera parte, se demuestra la corrección y equivalencia operacional de esta nueva semántica, así como se define un algoritmo de unificación mediante la reescritura de relaciones. La segunda parte de la tesis desarrolla una semántica para la programación lógica con restricciones usando la teoría de alegorías—versión categórica del álgebra de relaciones—de Freyd. Para ello, se definen dos nuevos conceptos de Categoría Regular de Lawvere y _-Alegoría, en las cuales es posible interpretar un programa lógico. La ventaja fundamental que el enfoque categórico aporta es la definición de una máquina categórica que mejora e sistema de reescritura presentado en la primera parte. Gracias al uso de relaciones tabulares, la máquina modela la ejecución eficiente sin salir de un marco estrictamente formal. Utilizando la reescritura de diagramas, se define un algoritmo para el cálculo de pullbacks en Categorías Regulares de Lawvere. Los dominios de las tabulaciones aportan información sobre la utilización de memoria y variable libres, mientras que el estado compartido queda capturado por los diagramas. La especificación de la máquina induce la derivación formal de un juego de instrucciones eficiente. El marco categórico aporta otras importantes ventajas, como la posibilidad de incorporar tipos de datos algebraicos, funciones y otras extensiones a Prolog, a la vez que se conserva el carácter 100% declarativo de nuestra semántica. ABSTRACT The calculus of binary relations was introduced by De Morgan in 1860, to be greatly developed by Peirce and Schröder, as well as many others in the twentieth century. Using different formulations of relational structures, Tarski, Givant, Freyd, and Scedrov have shown how relation algebras can provide a variable-free way of formalizing first order logic, higher order logic and set theory, among other formal systems. Building on those mathematical results, we develop denotational and operational semantics for Constraint Logic Programming using relation algebra. The idea of executable semantics plays a fundamental role in this work, both as a philosophical and technical foundation. We call a semantics executable when program execution can be carried out using the regular theory and tools that define the semantic universe. Throughout this work, the use of pure algebraic reasoning is the basis of denotational and operational results, eliminating all the classical non-equational meta-theory associated to traditional semantics for Logic Programming. All algebraic reasoning, including execution, is performed in an algebraic way, to the point we could state that the denotational semantics of a CLP program is directly executable. Techniques like optimization, partial evaluation and abstract interpretation find a natural place in our algebraic models. Other properties, like correctness of the implementation or program transformation are easy to check, as they are carried out using instances of the general equational theory. In the first part of the work, we translate Constraint Logic Programs to binary relations in a modified version of the distributive relation algebras used by Tarski. Execution is carried out by a rewriting system. We prove adequacy and operational equivalence of the semantics. In the second part of the work, the relation algebraic approach is improved by using allegory theory, a categorical version of the algebra of relations developed by Freyd and Scedrov. The use of allegories lifts the semantics to typed relations, which capture the number of logical variables used by a predicate or program state in a declarative way. A logic program is interpreted in a _-allegory, which is in turn generated from a new notion of Regular Lawvere Category. As in the untyped case, program translation coincides with program interpretation. Thus, we develop a categorical machine directly from the semantics. The machine is based on relation composition, with a pullback calculation algorithm at its core. The algorithm is defined with the help of a notion of diagram rewriting. In this operational interpretation, types represent information about memory allocation and the execution mechanism is more efficient, thanks to the faithful representation of shared state by categorical projections. We finish the work by illustrating how the categorical semantics allows the incorporation into Prolog of constructs typical of Functional Programming, like abstract data types, and strict and lazy functions.

Técnicas de procesado digital de señal aplicadas a acelerómetros

En este proyecto se estudian y analizan las diferentes técnicas de procesado digital de señal aplicadas a acelerómetros. Se hace uso de una tarjeta de prototipado, basada en DSP, para realizar las diferentes pruebas. El proyecto se basa, principalmente, en realizar filtrado digital en señales provenientes de un acelerómetro en concreto, el 1201F, cuyo campo de aplicación es básicamente la automoción. Una vez estudiadas la teoría de procesado y las características de los filtros, diseñamos una aplicación basándonos sobre todo en el entorno en el que se desarrollaría una aplicación de este tipo. A lo largo del diseño, se explican las diferentes fases: diseño por ordenador (Matlab), diseño de los filtros en el DSP (C), pruebas sobre el DSP sin el acelerómetro, calibración del acelerómetro, pruebas finales sobre el acelerómetro... Las herramientas utilizadas son: la plataforma Kit de evaluación 21-161N de Analog Devices (equipado con el entorno de desarrollo Visual DSP 4.5++), el acelerómetro 1201F, el sistema de calibración de acelerómetros CS-18-LF de Spektra y los programas software MATLAB 7.5 y CoolEditPRO 2.0. Se realizan únicamente filtros IIR de 2º orden, de todos los tipos (Butterworth, Chebyshev I y II y Elípticos). Realizamos filtros de banda estrecha, paso-banda y banda eliminada, de varios tipos, dentro del fondo de escala que permite el acelerómetro. Una vez realizadas todas las pruebas, tanto simulaciones como físicas, se seleccionan los filtros que presentan un mejor funcionamiento y se analizan para obtener conclusiones. Como se dispone de un entorno adecuado para ello, se combinan los filtros entre sí de varias maneras, para obtener filtros de mayor orden (estructura paralelo). De esta forma, a partir de filtros paso-banda, podemos obtener otras configuraciones que nos darán mayor flexibilidad. El objetivo de este proyecto no se basa sólo en obtener buenos resultados en el filtrado, sino también de aprovechar las facilidades del entorno y las herramientas de las que disponemos para realizar el diseño más eficiente posible. In this project, we study and analize digital signal processing in order to design an accelerometer-based application. We use a hardware card of evaluation, based on DSP, to make different tests. This project is based in design digital filters for an automotion application. The accelerometer type is 1201F. First, we study digital processing theory and main parameters of real filters, to make a design based on the application environment. Along the application, we comment all the different steps: computer design (Matlab), filter design on the DSP (C language), simulation test on the DSP without the accelerometer, accelerometer calibration, final tests on the accelerometer... Hardware and software tools used are: Kit of Evaluation 21-161-N, based on DSP, of Analog Devices (equiped with software development tool Visual DSP 4.5++), 1201-F accelerometer, CS-18-LF calibration system of SPEKTRA and software tools MATLAB 7.5 and CoolEditPRO 2.0. We only perform 2nd orden IIR filters, all-type : Butterworth, Chebyshev I and II and Ellyptics. We perform bandpass and stopband filters, with very narrow band, taking advantage of the accelerometer's full scale. Once all the evidence, both simulations and physical, are finished, filters having better performance and analyzed and selected to draw conclusions. As there is a suitable environment for it, the filters are combined together in different ways to obtain higher order filters (parallel structure). Thus, from band-pass filters, we can obtain many configurations that will give us greater flexibility. The purpose of this project is not only based on good results in filtering, but also to exploit the facilities of the environment and the available tools to make the most efficient design possible.

Acoustic displacement triangle based on the individual element test

A three node, displacement based, acoustic element is developed. In order to avoid spurious rotational modes, a higher order stiffness is introduced. The higher order stiffness is developed from an incompatible strain field which computes element volume changes under nodal rotational displacements fields. The higher order strain satisfies the IET requirements, non affecting convergence. The higher order stiffness is modulated, element by element, with a factor. Thus, the displacement based formulation is capable of placing the spurious rotational modes over the range of physical compressional modes that can be accurately captured by the mesh.