Constitutively active cAMP receptor mutants dominantly inhibit receptor-mediated signaling pathways in Dictyostelium discoideum

Dictyostelium, a soil amoeba, is able to develop from free-living cells to multicellular fruiting bodies upon starvation using extracellular cAMP to mediate cell-cell communication, chemotaxis and developmental gene expression. The seven transmembrane G protein-coupled cAMP receptor-1 (cAR1) mediated responses, such as the activation of adenylyl cyclase and guanylyl cyclase, are transient, due to the existence of poorly understood adaptation mechanisms. For this dissertation, the powerful genetics of the Dictyostelium system was employed to study the adaptation mechanism of cAR1-mediated cAMP signaling as well as mechanisms intrinsic to cAR1 that regulate its activation. ^ We proposed that constitutively active cAR1 would cause constant adaptation, thus inhibiting downstream pathways that are essential for aggregation and development. Therefore, a screen for dominant negative cAR1 mutants was undertaken to identify constitutively active receptor mutants. Three dominant negative cAR1 mutants were identified. All appear to be constitutively active receptor mutants because they are constitutively phosphorylated and possess high affinity for cAMP. Biochemical studies showed that these mutant receptors prevented the activation of downstream effectors, including adenylyl and guanylyl cyclases. In addition, these cells also were defective in cAMP chemotaxis and cAR1-mediated gene expression. These findings suggest that the mutant receptors block development by constantly activating multiple adaptation pathways. ^ Sequence analysis revealed that these mutations (I104N, L100H) are clustered in a conserved region of the third transmembrane helix (TM3) of cAR1. To investigate the role of this region in receptor activation, one of these residues, I104, was mutated to all the other 19 possible amino acids. We found that all but the most conservative substitutions increase the receptor's affinity about 20- to 70-fold. However, only highly polar substitutions of I104, particularly basic residues, resulted in receptors that are constitutively phosphorylated and dominantly inhibit development, suggesting that highly polar substitutions not only disrupt an interaction constraining the receptor in its low-affinity, inactive state but also promote an additional conformational change that resembles the ligand-bound conformation. Our findings suggest that I104 plays a specific role in constraining the receptor in its inactive state and that substituting it with highly polar residues results in constitutive activation. ^

Description and chemical and mineral composition of iron oxide samples from two Finnish lakes

Fifteen iron oxide accumulations from the bottoms of two Finnish lakes ("lake ores") were found to contain as much as 50% Fe. Differential X-ray powder diffraction and selective dissolution by oxalate showed that the samples consisted of poorly crystallized goethite and ferrihydrite. The crust ores of one lake had higher ferrihydrite to goethite ratios than the nodular ores of the other lake. The higher ferrihydrite proportion was attributed to a higher rate of Fe2+ supply from the ground water and/or a higher rate of oxidation as a function of water depth and bottom-sediment permeability. Values of Al-for-Fe substitution of the goethites determined from unit-cell dimensions agreed with those obtained from chemical extraction if the unit-cell volume rather than the c dimension was used. In very small goethite crystals a slight expansion of the a unit-cell dimension is probaby compensated by a corresponding contraction of the c dimension, so that a contraction of the c dimension need not necessarily be caused by Al substitution. The goethites of the two lakes differed significantly in their Al-for-Fe substitutions and hence in their unit-cell sizes, OH-bending characteristics, dehydroxylation temperatures, dissolution kinetics, and Mössbauer parameters. The difference in Al substitution (0 vs. 7 mole %) is attributed to the Al-supplying power of the bottom sediments: the silty-clayey sediments in one lake appear to have supplied A1 during goethite formation, whereas the gravelly-sandy sediments in the other lake did not. The compositions of the goethites thus reflect their environments of formation.

El mundo indígena frente a la dominación estatal. Norpatagonia, fines del siglo XIX - principios del siglo XX

El objetivo del presente trabajo es el análisis de las transformaciones del mundo indígena durante los años inmediatamente posteriores a las Campañas Militares de fines del siglo XIX, destacando sus estrategias de adaptación ante la nueva relación con el Estado Nacional. Así, los cambios en la organización sociopolítica indígena y en sus relaciones económicas en virtud de su nueva articulación con la sociedad estatal, son enfocados a través de diferentes estudios de caso: tribus sometidas voluntariamente y relocalizadas en tierras asignadas por el Estado; y grupos familiares que, a pesar de estar aislados de sus vínculos tribales tradicionales, mantuvieron su identidad étnica y cierto grado de autonomía social y económica. Los casos se desarrollan en el territorio de la actual provincia de Neuquén, entre 1882 y 1919, y son reconstruidos gracias a documentos de los archivos Histórico Provincial y de Tierras y Colonias de la provincia de Neuquén. Estas situaciones presentan una compleja dinámica en la cual la diversidad de continuidades, reemplazos y desapariciones queda integrada dentro de una misma lógica de supervivencia, traspasando la visión tradicional de una contradicción entre resistencia y asimilación.

Cambaceres, lector de Potpourri : 1882-1883

Las dos primeras ediciones de Potpourri. Silbidos de un vago aparecieron en octubre y noviembre de 1882; la tercera se publicó en diciembre del 83. Para la segunda, salvo la corrección de cinco erratas, el autor no introdujo ningún cambio. Sí lo hizo para la publicación de la tercera; el más importante: el agregado de un prólogo. En cuanto al resto del texto, el tipo de intervenciones -sustituciones léxicas y modificaciones formales que en ocasiones involucran transformaciones semánticas, ajustes que benefician la coherencia de la trama y la legibilidad- revela una preocupación evidente por el detalle

El mundo indígena frente a la dominación estatal. Norpatagonia, fines del siglo XIX - principios del siglo XX

El objetivo del presente trabajo es el análisis de las transformaciones del mundo indígena durante los años inmediatamente posteriores a las Campañas Militares de fines del siglo XIX, destacando sus estrategias de adaptación ante la nueva relación con el Estado Nacional. Así, los cambios en la organización sociopolítica indígena y en sus relaciones económicas en virtud de su nueva articulación con la sociedad estatal, son enfocados a través de diferentes estudios de caso: tribus sometidas voluntariamente y relocalizadas en tierras asignadas por el Estado; y grupos familiares que, a pesar de estar aislados de sus vínculos tribales tradicionales, mantuvieron su identidad étnica y cierto grado de autonomía social y económica. Los casos se desarrollan en el territorio de la actual provincia de Neuquén, entre 1882 y 1919, y son reconstruidos gracias a documentos de los archivos Histórico Provincial y de Tierras y Colonias de la provincia de Neuquén. Estas situaciones presentan una compleja dinámica en la cual la diversidad de continuidades, reemplazos y desapariciones queda integrada dentro de una misma lógica de supervivencia, traspasando la visión tradicional de una contradicción entre resistencia y asimilación.

Cambaceres, lector de Potpourri : 1882-1883

Las dos primeras ediciones de Potpourri. Silbidos de un vago aparecieron en octubre y noviembre de 1882; la tercera se publicó en diciembre del 83. Para la segunda, salvo la corrección de cinco erratas, el autor no introdujo ningún cambio. Sí lo hizo para la publicación de la tercera; el más importante: el agregado de un prólogo. En cuanto al resto del texto, el tipo de intervenciones -sustituciones léxicas y modificaciones formales que en ocasiones involucran transformaciones semánticas, ajustes que benefician la coherencia de la trama y la legibilidad- revela una preocupación evidente por el detalle

El mundo indígena frente a la dominación estatal. Norpatagonia, fines del siglo XIX - principios del siglo XX

El objetivo del presente trabajo es el análisis de las transformaciones del mundo indígena durante los años inmediatamente posteriores a las Campañas Militares de fines del siglo XIX, destacando sus estrategias de adaptación ante la nueva relación con el Estado Nacional. Así, los cambios en la organización sociopolítica indígena y en sus relaciones económicas en virtud de su nueva articulación con la sociedad estatal, son enfocados a través de diferentes estudios de caso: tribus sometidas voluntariamente y relocalizadas en tierras asignadas por el Estado; y grupos familiares que, a pesar de estar aislados de sus vínculos tribales tradicionales, mantuvieron su identidad étnica y cierto grado de autonomía social y económica. Los casos se desarrollan en el territorio de la actual provincia de Neuquén, entre 1882 y 1919, y son reconstruidos gracias a documentos de los archivos Histórico Provincial y de Tierras y Colonias de la provincia de Neuquén. Estas situaciones presentan una compleja dinámica en la cual la diversidad de continuidades, reemplazos y desapariciones queda integrada dentro de una misma lógica de supervivencia, traspasando la visión tradicional de una contradicción entre resistencia y asimilación.

Cambaceres, lector de Potpourri : 1882-1883

Las dos primeras ediciones de Potpourri. Silbidos de un vago aparecieron en octubre y noviembre de 1882; la tercera se publicó en diciembre del 83. Para la segunda, salvo la corrección de cinco erratas, el autor no introdujo ningún cambio. Sí lo hizo para la publicación de la tercera; el más importante: el agregado de un prólogo. En cuanto al resto del texto, el tipo de intervenciones -sustituciones léxicas y modificaciones formales que en ocasiones involucran transformaciones semánticas, ajustes que benefician la coherencia de la trama y la legibilidad- revela una preocupación evidente por el detalle

Magnetic properties of ODP Hole 109-648B

Seventeen samples from pillow or massive "zero age" fresh basalts from ODP Legs 106 and 109 were studied in order to examine their magnetic properties and oxidation degree. Thermomagnetic analyses of studied samples show Curie temperatures from 127°C to 220°C with reversible heating and cooling curves. Hysteresis parameters indicate the contribution of large Pseudo-Single Domain (PSD) grain of titanomagnetites with saturation magnetization between 0.4 and 0.7 emu/g which is almost twice that those of other recent mid-oceanic dredged basalts (e.g., FAMOUS and CYAMEX-RISE). The large grain sizes and higher magnetic mineral concentration may suggest a slower cooling of these basalts compared to those previously studied. Electron microprobe analyses of titanomagnetite grains combined with Curie point determinations give z = 0.3 for the degree of low temperature oxidation, which is close to the other values reported for low temperature oxidation of mid-oceanic ridge basalts.

Trioctahedral micas in xenolithic ejecta from recent volcanism of the Somma-Vesuvius

This study reports the first crystal chemical database resulting from a detailed structural investigation of trioctahedral micas found in xenolithic ejecta produced during the AD 1631, 1872 and 1944 eruptions, three explosive episodes of recent volcanic period of Vesuvius volcano (Southern Italy). Three xenolith types were selected: metamorphic/metasomatic skarns, pyrometamorphic/hydrothermally altered nodules and mafic cumulates. They are related to different magma chemistry and effusive styles: from sub-plinian and most evolved (AD 1631 eruption) to violent strombolian with medium evolution degree (AD 1872 eruption) to vulcanian-effusive, least evolved (AD 1944 eruption) event, respectively. Both xenoliths and micas were investigated employing multiple techniques: the xenoliths were characterized by X-ray fluorescence, inductively-coupled plasma-mass spectrometry, optical microscopy, X-ray powder diffraction, and quantitative energy-dispersive microanalysis; the micas were studied by electron probe microanalysis and single crystal X-ray diffraction. The mica-bearing xenoliths show variable texture and mineralogical assemblage, clearly related to their different origin. Based on the major oxide chemistry, only one xenolithic sample falls in the skarn compositional field from the Somma-Vesuvius literature, some fall close to the skarns and cumulate fields, others plot close to the syenite/foidolite/essexite field. A subgroup of the selected ejecta does not fall or approach any of the compositional fields. Trace and rare earth element patterns show some petrological affinity between studied xenoliths and erupted magmas with typical Eu, Ta and Nb negative anomalies. Strongly depleted patterns were detected for the 1631 metamorphic/metasomatic skarns xenoliths. Three distinct mica groups were distinguished: 1) Mg-, Al-rich, low Ti-bearing, low to moderate F-bearing varieties (1631 xenolith), 2) Al-moderate, F- and Mg-rich, Ti-, Fe-poor varieties (1872 xenolith), and 3) Al-, Ti- and Fe-rich, F-poor phases (1944 xenolith). All the analysed mica crystals are 1M polytypes with the expected space group C2/m. Micas from xenoliths of the 1631 Vesuvius eruption are phlogopites characterized by a combination of low extent of oxy-type and variable extent OH-F-substitutions, as testified by the range of F concentration (from ~ 0.20 to 0.80 apfu). Micas from xenoliths of the 1872 Vesuvius eruption exhibit structural peculiarities typical of fluorophlogopites, i.e. OH-F-substitution is predominant. Micas from the xenolith of the 1944 Vesuvius eruption display features typical of oxy-substituted micas. The variability of the crystal chemical features of the studied micas are consistent with the remarkable variation of their host rocks. Micas from 1631 nodules are related to metasomatic, skarn-type environment, deriving from the metamorphosed wall-rocks hosting the magma reservoir. The fluorophlogopites from the 1872 xenoliths testify for strongly dehydrated environmental conditions compared to those of the 1631 and 1944 hosts. Finally, magma storage condition at depth, associated to a decreasing aH2O may have promoted major oxy-type substitutions in 1944 biotites.

Trade Coefficients and the Role of Elasticity in a Spatial CGE Model Based on the Armington Assumption

The Armington Assumption in the context of multi-regional CGE models is commonly interpreted as follows: Same commodities with different origins are imperfect substitutes for each other. In this paper, a static spatial CGE model that is compatible with this assumption and explicitly considers the transport sector and regional price differentials is formulated. Trade coefficients, which are derived endogenously from the optimization behaviors of firms and households, are shown to take the form of a potential function. To investigate how the elasticity of substitutions affects equilibrium solutions, a simpler version of the model that incorporates three regions and two sectors (besides the transport sector) is introduced. Results indicate: (1) if commodities produced in different regions are perfect substitutes, regional economies will be either autarkic or completely symmetric and (2) if they are imperfect substitutes, the impact of elasticity on the price equilibrium system as well as trade coefficients will be nonlinear and sometimes very sensitive.

Abstract multiple specialization and its application to program parallelization.

Program specialization optimizes programs for known valúes of the input. It is often the case that the set of possible input valúes is unknown, or this set is infinite. However, a form of specialization can still be performed in such cases by means of abstract interpretation, specialization then being with respect to abstract valúes (substitutions), rather than concrete ones. We study the múltiple specialization of logic programs based on abstract interpretation. This involves in principie, and based on information from global analysis, generating several versions of a program predicate for different uses of such predicate, optimizing these versions, and, finally, producing a new, "multiply specialized" program. While múltiple specialization has received theoretical attention, little previous evidence exists on its practicality. In this paper we report on the incorporation of múltiple specialization in a parallelizing compiler and quantify its effects. A novel approach to the design and implementation of the specialization system is proposed. The resulting implementation techniques result in identical specializations to those of the best previously proposed techniques but require little or no modification of some existing abstract interpreters. Our results show that, using the proposed techniques, the resulting "abstract múltiple specialization" is indeed a relevant technique in practice. In particular, in the parallelizing compiler application, a good number of run-time tests are eliminated and invariants extracted automatically from loops, resulting generally in lower overheads and in several cases in increased speedups.

Compile-time derivation of variable dependency using abstract interpretation

Traditional schemes for abstract interpretation-based global analysis of logic programs generally focus on obtaining procedure argument mode and type information. Variable sharing information is often given only the attention needed to preserve the correctness of the analysis. However, such sharing information can be very useful. In particular, it can be used for predicting runtime goal independence, which can eliminate costly run-time checks in and-parallel execution. In this paper, a new algorithm for doing abstract interpretation in logic programs is described which concentrates on inferring the dependencies of the terms bound to program variables with increased precisión and at all points in the execution of the program, rather than just at a procedure level. Algorithms are presented for computing abstract entry and success substitutions which extensively keep track of variable aliasing and term dependence information. In addition, a new, abstract domain independent ñxpoint algorithm is presented and described in detail. The algorithms are illustrated with examples. Finally, results from an implementation of the abstract interpreter are presented.

Efficient top-down set-sharing analysis using cliques

Abstract. We study the problem of efficient, scalable set-sharing analysis of logic programs. We use the idea of representing sharing information as a pair of abstract substitutions, one of which is a worst-case sharing representation called a clique set, which was previously proposed for the case of inferring pair-sharing. We use the clique-set representation for (1) inferring actual set-sharing information, and (2) analysis within a top-down framework. In particular, we define the new abstract functions required by standard top-down analyses, both for sharing alone and also for the case of including freeness in addition to sharing. We use cliques both as an alternative representation and as widening, defining several widening operators. Our experimental evaluation supports the conclusión that, for inferring set-sharing, as it was the case for inferring pair-sharing, precisión losses are limited, while useful efficieney gains are obtained. We also derive useful conclusions regarding the interactions between thresholds, precisión, efficieney and cost of widening. At the limit, the clique-set representation allowed analyzing some programs that exceeded memory capacity using classical sharing representations.

Abstract specialization and its application to program parallelization

Program specialization optimizes programs for known valúes of the input. It is often the case that the set of possible input valúes is unknown, or this set is infinite. However, a form of specialization can still be performed in such cases by means of abstract interpretation, specialization then being with respect to abstract valúes (substitutions), rather than concrete ones. This paper reports on the application of abstract múltiple specialization to automatic program parallelization in the &-Prolog compiler. Abstract executability, the main concept underlying abstract specialization, is formalized, the design of the specialization system presented, and a non-trivial example of specialization in automatic parallelization is given.