Modular organization of the Friend murine leukemia virus envelope protein underlies the mechanism of infection

Retrovirus infection is initiated by receptor-dependent fusion of the envelope to the cell membrane. The modular organization of the envelope protein of C type retroviruses has been exploited to investigate how binding of the surface subunit (SU) to receptor triggers fusion mediated by the transmembrane (TM) subunit. We show that deletion of the receptor-binding domain (RBD) from SU of Friend murine leukemia virus (Fr-MLV) abolishes infection that is restored by supplying RBD as a soluble protein. Infection by this mechanism remains dependent on receptor expression. When membrane attachment of the virus lacking RBD is reestablished by inserting the hormone erythropoietin, infection remains dependent on the RBD/receptor complex. However, infection increases 50-fold to 5 × 105 units/ml on cells that also express the erythropoietin receptor. Soluble RBD from Fr-MLV also restores infection by amphotropic and xenotropic MLVs in which RBD is deleted. These experiments demonstrate that RBD has two functions: mediating virus attachment and activating the fusion mechanism. In addition, they indicate that receptor engagement triggers fusion by promoting a subgroup-independent functional interaction between RBD and the remainder of SU and/or TM.

Paper-like electronic displays: Large-area rubber-stamped plastic sheets of electronics and microencapsulated electrophoretic inks

Electronic systems that use rugged lightweight plastics potentially offer attractive characteristics (low-cost processing, mechanical flexibility, large area coverage, etc.) that are not easily achieved with established silicon technologies. This paper summarizes work that demonstrates many of these characteristics in a realistic system: organic active matrix backplane circuits (256 transistors) for large (≈5 × 5-inch) mechanically flexible sheets of electronic paper, an emerging type of display. The success of this effort relies on new or improved processing techniques and materials for plastic electronics, including methods for (i) rubber stamping (microcontact printing) high-resolution (≈1 μm) circuits with low levels of defects and good registration over large areas, (ii) achieving low leakage with thin dielectrics deposited onto surfaces with relief, (iii) constructing high-performance organic transistors with bottom contact geometries, (iv) encapsulating these transistors, (v) depositing, in a repeatable way, organic semiconductors with uniform electrical characteristics over large areas, and (vi) low-temperature (≈100°C) annealing to increase the on/off ratios of the transistors and to improve the uniformity of their characteristics. The sophistication and flexibility of the patterning procedures, high level of integration on plastic substrates, large area coverage, and good performance of the transistors are all important features of this work. We successfully integrate these circuits with microencapsulated electrophoretic “inks” to form sheets of electronic paper.

Parametrizations of elliptic curves by Shimura curves and by classical modular curves

Fix an isogeny class

SMART, a simple modular architecture research tool: Identification of signaling domains

Accurate multiple alignments of 86 domains that occur in signaling proteins have been constructed and used to provide a Web-based tool (SMART: simple modular architecture research tool) that allows rapid identification and annotation of signaling domain sequences. The majority of signaling proteins are multidomain in character with a considerable variety of domain combinations known. Comparison with established databases showed that 25% of our domain set could not be deduced from SwissProt and 41% could not be annotated by Pfam. SMART is able to determine the modular architectures of single sequences or genomes; application to the entire yeast genome revealed that at least 6.7% of its genes contain one or more signaling domains, approximately 350 greater than previously annotated. The process of constructing SMART predicted (i) novel domain homologues in unexpected locations such as band 4.1-homologous domains in focal adhesion kinases; (ii) previously unknown domain families, including a citron-homology domain; (iii) putative functions of domain families after identification of additional family members, for example, a ubiquitin-binding role for ubiquitin-associated domains (UBA); (iv) cellular roles for proteins, such predicted DEATH domains in netrin receptors further implicating these molecules in axonal guidance; (v) signaling domains in known disease genes such as SPRY domains in both marenostrin/pyrin and Midline 1; (vi) domains in unexpected phylogenetic contexts such as diacylglycerol kinase homologues in yeast and bacteria; and (vii) likely protein misclassifications exemplified by a predicted pleckstrin homology domain in a Candida albicans protein, previously described as an integrin.

Adjoint modular Galois representations and their Selmer groups

In the last 15 years, many class number formulas and main conjectures have been proven. Here, we discuss such formulas on the Selmer groups of the three-dimensional adjoint representation ad(φ) of a two-dimensional modular Galois representation φ. We start with the p-adic Galois representation φ0 of a modular elliptic curve E and present a formula expressing in terms of L(1, ad(φ0)) the intersection number of the elliptic curve E and the complementary abelian variety inside the Jacobian of the modular curve. Then we explain how one can deduce a formula for the order of the Selmer group Sel(ad(φ0)) from the proof of Wiles of the Shimura–Taniyama conjecture. After that, we generalize the formula in an Iwasawa theoretic setting of one and two variables. Here the first variable, T, is the weight variable of the universal p-ordinary Hecke algebra, and the second variable is the cyclotomic variable S. In the one-variable case, we let φ denote the p-ordinary Galois representation with values in GL2(Zp[[T]]) lifting φ0, and the characteristic power series of the Selmer group Sel(ad(φ)) is given by a p-adic L-function interpolating L(1, ad(φk)) for weight k + 2 specialization φk of φ. In the two-variable case, we state a main conjecture on the characteristic power series in Zp[[T, S]] of Sel(ad(φ) ⊗ ν−1), where ν is the universal cyclotomic character with values in Zp[[S]]. Finally, we describe our recent results toward the proof of the conjecture and a possible strategy of proving the main conjecture using p-adic Siegel modular forms.

Congruences between modular forms: Raising the level and dropping Euler factors

We discuss the relationship among certain generalizations of results of Hida, Ribet, and Wiles on congruences between modular forms. Hida’s result accounts for congruences in terms of the value of an L-function, and Ribet’s result is related to the behavior of the period that appears there. Wiles’ theory leads to a class number formula relating the value of the L-function to the size of a Galois cohomology group. The behavior of the period is used to deduce that a formula at “nonminimal level” is obtained from one at “minimal level” by dropping Euler factors from the L-function.

Modular organization of intrinsic connections associated with spectral tuning in cat auditory cortex

Many response properties in primary auditory cortex (AI) are segregated spatially and organized topographically as those in primary visual cortex. Intensive study has not revealed an intrinsic, anatomical organizing principle related to an AI functional topography. We used retrograde anatomic tracing and topographic physiologic mapping of acoustic response properties to reveal long-range (≥1.5 mm) convergent intrinsic horizontal connections between AI subregions with similar bandwidth and characteristic frequency selectivity. This suggests a modular organization for processing spectral bandwidth in AI.

Modular construction for function of a ribonucleoprotein enzyme: the catalytic domain of Bacillus subtilis RNase P complexed with B.subtilis RNase P protein

The bacterial RNase P holoenzyme catalyzes the formation of the mature 5′-end of tRNAs and is composed of an RNA and a protein subunit. Among the two folding domains of the RNase P RNA, the catalytic domain (C-domain) contains the active site of this ribozyme. We investigated specific binding of the Bacillus subtilis C-domain with the B.subtilis RNase P protein and examined the catalytic activity of this C-domain–P protein complex. The C-domain forms a specific complex with the P protein with a binding constant of ∼0.1 µM. The C-domain–P protein complex and the holoenzyme are equally efficient in cleaving single-stranded RNA (∼0.9 min–1 at pH 7.8) and substrates with a hairpin–loop 3′ to the cleavage site (∼40 min–1). The holoenzyme reaction is much more efficient with a pre-tRNA substrate, binding at least 100-fold better and cleaving 10–500 times more efficiently. These results demonstrate that the RNase P holoenzyme is functionally constructed in three parts. The catalytic domain alone contains the active site, but has little specificity and affinity for most substrates. The specificity and affinity for the substrate is generated by either the specificity domain of RNase P RNA binding to a T stem–loop-like hairpin or RNase P protein binding to a single-stranded RNA. This modular construction may be exploited to obtain RNase P-based ribonucleoprotein complexes with altered substrate specificity.

A modular misexpression screen in Drosophila detecting tissue-specific phenotypes.

Genetic screens in Drosophila have lead to the discovery of many genes important for patterning and signal transduction in diverse organisms. Traditionally, the phenotypic effects of loss-of-function mutations are analyzed. As an alternative way to link genes and function, I have developed a versatile misexpression screen in Drosophila, the first such screen in higher eukaryotes. The screen identifies genes that, when over- or misexpressed in a pattern of interest, give a specific phenotype or modulate an existing mutant phenotype. It is based on Gal4 transactivation of a mobile enhancer and promoter that "targets" random endogenous genes for expression. The modular design of the screen allows directed expression in any temporal or spatial pattern. When activated in the developing eye, 4% of target inserts gave dominant phenotypes. One insertion was in the gene encoding Ras GTPase-activating protein; its overexpression phenotype was strongly enhanced by a mutation in Ras1. Thus, biologically relevant phenotypes and genetic interactions are identified using this method. The screen is a powerful new tool for developmental genetics; similar approaches can also be developed for other organisms.

Modular cis-regulatory organization of developmentally expressed genes: two genes transcribed territorially in the sea urchin embryo, and additional examples.

The cis-regulatory systems that control developmental expression of two sea urchin genes have been subjected to detailed functional analysis. Both systems are modular in organization: specific, separable fragments of the cis-regulatory DNA each containing multiple transcription factor target sites execute particular regulatory subfunctions when associated with reporter genes and introduced into the embryo. The studies summarized here were carried out on the CyIIIa gene, expressed in the embryonic aboral ectoderm and on the Endo16 gene, expressed in the embryonic vegetal plate, archenteron, and then midgut. The regulatory systems of both genes include modules that control particular aspects of temporal and spatial expression, and in both the territorial boundaries of expression depend on a combination of negative and positive functions. In both genes different regulatory modules control early and late embryonic expression. Modular cis-regulatory organization is widespread in developmentally regulated genes, and we present a tabular summary that includes many examples from mouse and Drosophila. We regard cis-regulatory modules as units of developmental transcription control, and also of evolution, in the assembly of transcription control systems.

COMPENDIUM: una herramienta de generación de resúmenes modular

En este artículo presentamos COMPENDIUM, una herramienta de generación de resúmenes de textos modular. Esta herramienta se compone de un módulo central con cinco etapas bien diferenciadas: i) análisis lingüístico; ii) detección de redundancia; iii) identificación del tópico; iv) detección de relevancia; y v) generación del resumen, y una serie de módulos adicionales que permiten incrementar las funcionalidades de la herramienta permitiendo la generación de distintos tipos de resúmenes, como por ejemplo orientados a un tema concreto. Realizamos una evaluación exhaustiva en dos dominios distintos (noticias de prensa y documentos sobre lugares turísticos) y analizamos diferentes tipos de resúmenes generados con COMPENDIUM (mono-documento, multi-documento, genéricos y orientados a un tema). Además, comparamos nuestro sistema con otros sistemas de generación de resúmenes actuales. Los resultados que se obtienen demuestran que la herramienta COMPENDIUM es capaz de generar resúmenes competitivos para los distintos tipos de resúmenes propuestos.

Integration of modular process simulators under the Generalized Disjunctive Programming framework for the structural flowsheet optimization

The optimization of chemical processes where the flowsheet topology is not kept fixed is a challenging discrete-continuous optimization problem. Usually, this task has been performed through equation based models. This approach presents several problems, as tedious and complicated component properties estimation or the handling of huge problems (with thousands of equations and variables). We propose a GDP approach as an alternative to the MINLP models coupled with a flowsheet program. The novelty of this approach relies on using a commercial modular process simulator where the superstructure is drawn directly on the graphical use interface of the simulator. This methodology takes advantage of modular process simulators (specially tailored numerical methods, reliability, and robustness) and the flexibility of the GDP formulation for the modeling and solution. The optimization tool proposed is successfully applied to the synthesis of a methanol plant where different alternatives are available for the streams, equipment and process conditions.

La enseñanza de robótica en el Máster en Automática y Robótica mediante un robot modular

Este trabajo muestra cómo se realiza la enseñanza de robótica mediante un robot modular y los resultados educativos obtenidos en el Máster Universitario en Automática y Robótica de la Escuela Politécnica Superior de la Universidad de Alicante. En el artículo se describen los resultados obtenidos con el uso de este robot modular tanto en competencias genéricas como específicas, en las enseñanzas de electrónica, control y programación del Máster. En este artículo se exponen los objetivos de aprendizaje para cada uno de ellos, su aplicación a la enseñanza y los resultados educativos obtenidos. En los resultados del estudio, cabe destacar que el alumno ha mostrado mayor interés y ha fomentado su aprendizaje autónomo. Para ello, el robot modular se construyó con herramientas para fomentar este tipo de enseñanza y aprendizaje, tales como comunicaciones interactivas para monitorizar, cambiar y adaptar diversos parámetros de control y potencia del robot.

Desarrollo de un robot modular para la enseñanza en el Máster en Automática y Robótica

Este trabajo presenta el diseño, construcción y programación de un robot modular para el desarrollo tanto de competencias genéricas como específicas, en las enseñanzas de electrónica, control y programación del Master de Automática y Robótica de la Escuela Politécnica Superior de la Universidad de Alicante. En este trabajo se exponen los diferentes módulos propuestos, así como los objetivos de aprendizaje para cada uno de ellos. Uno de los factores más importantes a destacar en el presente estudio es el posible desarrollo de la creatividad y el aprendizaje autónomo. Para ello, se desarrollará especialmente un módulo de comunicación por bluetooth que servirá para monitorizar, cambiar y adaptar on-line diversos parámetros de control y potencia del robot. Además, dicha herramienta se ha introducido como parte de la metodología en las asignaturas del Máster de Electromecánica y Sistemas de Control Automático. En esta memoria se mostrarán los distintos resultados obtenidos durante y en la finalización de este trabajo.