Leibniz y el concepto de analogía

En este trabajo se aborda un análisis de las aplicaciones leibnizianas de la analogía y del razonamiento analógico. De este modo, se trata de mostrar que el concepto de analogía leibniziano se funda en la idea de semejanza estructural. A partir de esta consideración, se abordan dos maneras básicas en que Leibniz aplica el razonamiento analógico. La primera es de carácter conjetural y posee un valor heurístico, mientras que la segunda constituye un tipo de razonamiento analógicodemostrativo,al menosen suintención,puesto que trata de fundamentar las conclusiones dentro de un ámbito teórico a partir de unprincipio de transferencia fundado en la identidad de propiedades estructurales.Este procedimiento se ejemplifica por medio de una presentación general de laconcepción leibniziana de las verdades contingentes. De este modo, el trabajo concluye señalando la importancia teórica del concepto de semejanza en el pensamiento leibiniziano.

Leibniz y el concepto de analogía

En este trabajo se aborda un análisis de las aplicaciones leibnizianas de la analogía y del razonamiento analógico. De este modo, se trata de mostrar que el concepto de analogía leibniziano se funda en la idea de semejanza estructural. A partir de esta consideración, se abordan dos maneras básicas en que Leibniz aplica el razonamiento analógico. La primera es de carácter conjetural y posee un valor heurístico, mientras que la segunda constituye un tipo de razonamiento analógicodemostrativo,al menosen suintención,puesto que trata de fundamentar las conclusiones dentro de un ámbito teórico a partir de unprincipio de transferencia fundado en la identidad de propiedades estructurales.Este procedimiento se ejemplifica por medio de una presentación general de laconcepción leibniziana de las verdades contingentes. De este modo, el trabajo concluye señalando la importancia teórica del concepto de semejanza en el pensamiento leibiniziano.

Leibniz y el concepto de analogía

En este trabajo se aborda un análisis de las aplicaciones leibnizianas de la analogía y del razonamiento analógico. De este modo, se trata de mostrar que el concepto de analogía leibniziano se funda en la idea de semejanza estructural. A partir de esta consideración, se abordan dos maneras básicas en que Leibniz aplica el razonamiento analógico. La primera es de carácter conjetural y posee un valor heurístico, mientras que la segunda constituye un tipo de razonamiento analógicodemostrativo,al menosen suintención,puesto que trata de fundamentar las conclusiones dentro de un ámbito teórico a partir de unprincipio de transferencia fundado en la identidad de propiedades estructurales.Este procedimiento se ejemplifica por medio de una presentación general de laconcepción leibniziana de las verdades contingentes. De este modo, el trabajo concluye señalando la importancia teórica del concepto de semejanza en el pensamiento leibiniziano.

Estudio de calidad de codificación utilizando los perfiles 10 Bits del estándar H.264

Desde los inicios de la codificación de vídeo digital hasta hoy, tanto la señal de video sin comprimir de entrada al codificador como la señal de salida descomprimida del decodificador, independientemente de su resolución, uso de submuestreo en los planos de diferencia de color, etc. han tenido siempre la característica común de utilizar 8 bits para representar cada una de las muestras. De la misma manera, los estándares de codificación de vídeo imponen trabajar internamente con estos 8 bits de precisión interna al realizar operaciones con las muestras cuando aún no se han transformado al dominio de la frecuencia. Sin embargo, el estándar H.264, en gran auge hoy en día, permite en algunos de sus perfiles orientados al mundo profesional codificar vídeo con más de 8 bits por muestra. Cuando se utilizan estos perfiles, las operaciones efectuadas sobre las muestras todavía sin transformar se realizan con la misma precisión que el número de bits del vídeo de entrada al codificador. Este aumento de precisión interna tiene el potencial de permitir unas predicciones más precisas, reduciendo el residuo a codificar y aumentando la eficiencia de codificación para una tasa binaria dada. El objetivo de este Proyecto Fin de Carrera es estudiar, utilizando las medidas de calidad visual objetiva PSNR (Peak Signal to Noise Ratio, relación señal ruido de pico) y SSIM (Structural Similarity, similaridad estructural), el efecto sobre la eficiencia de codificación y el rendimiento al trabajar con una cadena de codificación/descodificación H.264 de 10 bits en comparación con una cadena tradicional de 8 bits. Para ello se utiliza el codificador de código abierto x264, capaz de codificar video de 8 y 10 bits por muestra utilizando los perfiles High, High 10, High 4:2:2 y High 4:4:4 Predictive del estándar H.264. Debido a la ausencia de herramientas adecuadas para calcular las medidas PSNR y SSIM de vídeo con más de 8 bits por muestra y un tipo de submuestreo de planos de diferencia de color distinto al 4:2:0, como parte de este proyecto se desarrolla también una aplicación de análisis en lenguaje de programación C capaz de calcular dichas medidas a partir de dos archivos de vídeo sin comprimir en formato YUV o Y4M. ABSTRACT Since the beginning of digital video compression, the uncompressed video source used as input stream to the encoder and the uncompressed decoded output stream have both used 8 bits for representing each sample, independent of resolution, chroma subsampling scheme used, etc. In the same way, video coding standards force encoders to work internally with 8 bits of internal precision when working with samples before being transformed to the frequency domain. However, the H.264 standard allows coding video with more than 8 bits per sample in some of its professionally oriented profiles. When using these profiles, all work on samples still in the spatial domain is done with the same precision the input video has. This increase in internal precision has the potential of allowing more precise predictions, reducing the residual to be encoded, and thus increasing coding efficiency for a given bitrate. The goal of this Project is to study, using PSNR (Peak Signal to Noise Ratio) and SSIM (Structural Similarity) objective video quality metrics, the effects on coding efficiency and performance caused by using an H.264 10 bit coding/decoding chain compared to a traditional 8 bit chain. In order to achieve this goal the open source x264 encoder is used, which allows encoding video with 8 and 10 bits per sample using the H.264 High, High 10, High 4:2:2 and High 4:4:4 Predictive profiles. Given that no proper tools exist for computing PSNR and SSIM values of video with more than 8 bits per sample and chroma subsampling schemes other than 4:2:0, an analysis application written in the C programming language is developed as part of this Project. This application is able to compute both metrics from two uncompressed video files in the YUV or Y4M format.

The RIIβ regulatory subunit of protein kinase A binds to cAMP response element: An alternative cAMP signaling pathway

cAMP, through the activation of cAMP-dependent protein kinase (PKA), is involved in transcriptional regulation. In eukaryotic cells, cAMP is not considered to alter the binding affinity of CREB/ATF to cAMP-responsive element (CRE) but to induce serine phosphorylation and consequent increase in transcriptional activity. In contrast, in prokaryotic cells, cAMP enhances the DNA binding of the catabolite repressor protein to regulate the transcription of several operons. The structural similarity of the cAMP binding sites in catabolite repressor protein and regulatory subunit of PKA type II (RII) suggested the possibility of a similar role for RII in eukaryotic gene regulation. Herein we report that RIIβ subunit of PKA is a transcription factor capable of interacting physically and functionally with a CRE. In contrast to CREB/ATF, the binding of RIIβ to a CRE was enhanced by cAMP, and in addition, RIIβ exhibited transcriptional activity as a Gal4-RIIβ fusion protein. These experiments identify RIIβ as a component of an alternative pathway for regulation of CRE-directed transcription in eukaryotic cells.

Comparison of the ion channel characteristics of proapoptotic BAX and antiapoptotic BCL-2

The BCL-2 family of proteins is composed of both pro- and antiapoptotic regulators, although its most critical biochemical functions remain uncertain. The structural similarity between the BCL-XL monomer and several ion-pore-forming bacterial toxins has prompted electrophysiologic studies. Both BAX and BCL-2 insert into KCl-loaded vesicles in a pH-dependent fashion and demonstrate macroscopic ion efflux. Release is maximum at ≈pH 4.0 for both proteins; however, BAX demonstrates a broader pH range of activity. Both purified proteins also insert into planar lipid bilayers at pH 4.0. Single-channel recordings revealed a minimal channel conductance for BAX of 22 pS that evolved to channel currents with at least three subconductance levels. The final, apparently stable BAX channel had a conductance of 0.731 nS at pH 4.0 that changed to 0.329 nS when shifted to pH 7.0 but remained mildly Cl− selective and predominantly open. When BAX-incorporated lipid vesicles were fused to planar lipid bilayers at pH 7.0, a Cl−-selective (PK/PCl = 0.3) 1.5-nS channel displaying mild inward rectification was noted. In contrast, BCL-2 formed mildly K+-selective (PK/PCl = 3.9) channels with a most prominent initial conductance of 80 pS that increased to 1.90 nS. Fusion of BCL-2-incorporated lipid vesicles into planar bilayers at pH 7.0 also revealed mild K+ selectivity (PK/PCl = 2.4) with a maximum conductance of 1.08 nS. BAX and BCL-2 each form channels in artificial membranes that have distinct characteristics including ion selectivity, conductance, voltage dependence, and rectification. Thus, one role of these molecules may include pore activity at selected membrane sites.

Rational engineering of a miniprotein that reproduces the core of the CD4 site interacting with HIV-1 envelope glycoprotein

Protein–protein interacting surfaces are usually large and intricate, making the rational design of small mimetics of these interfaces a daunting problem. On the basis of a structural similarity between the CDR2-like loop of CD4 and the β-hairpin region of a short scorpion toxin, scyllatoxin, we transferred the side chains of nine residues of CD4, central in the binding to HIV-1 envelope glycoprotein (gp120), to a structurally homologous region of the scorpion toxin scaffold. In competition experiments, the resulting 27-amino acid miniprotein inhibited binding of CD4 to gp120 with a 40 μM IC50. Structural analysis by NMR showed that both the backbone of the chimeric β-hairpin and the introduced side chains adopted conformations similar to those of the parent CD4. Systematic single mutations suggested that most CD4 residues from the CDR2-like loop were reproduced in the miniprotein, including the critical Phe-43. The structural and functional analysis performed suggested five additional mutations that, once incorporated in the miniprotein, increased its affinity for gp120 by 100-fold to an IC50 of 0.1–1.0 μM, depending on viral strains. The resulting mini-CD4 inhibited infection of CD4+ cells by different virus isolates. Thus, core regions of large protein–protein interfaces can be reproduced in miniprotein scaffolds, offering possibilities for the development of inhibitors of protein–protein interactions that may represent useful tools in biology and in drug discovery.

Proteolytic Processing and Ca2+-binding Activity of Dense-Core Vesicle Polypeptides in Tetrahymena

Formation and discharge of dense-core secretory vesicles depend on controlled rearrangement of the core proteins during their assembly and dispersal. The ciliate Tetrahymena thermophila offers a simple system in which the mechanisms may be studied. Here we show that most of the core consists of a set of polypeptides derived proteolytically from five precursors. These share little overall amino acid identity but are nonetheless predicted to have structural similarity. In addition, sites of proteolytic processing are notably conserved and suggest that specific endoproteases as well as carboxypeptidase are involved in core maturation. In vitro binding studies and sequence analysis suggest that the polypeptides bind calcium in vivo. Core assembly and postexocytic dispersal are compartment-specific events. Two likely regulatory factors are proteolytic processing and exposure to calcium. We asked whether these might directly influence the conformations of core proteins. Results using an in vitro chymotrypsin accessibility assay suggest that these factors can induce sequential structural rearrangements. Such progressive changes in polypeptide folding may underlie the mechanisms of assembly and of rapid postexocytic release. The parallels between dense-core vesicles in different systems suggest that similar mechanisms are widespread in this class of organelles.

Hox cluster genomics in the horn shark, Heterodontus francisci

Reconstructing the evolutionary history of Hox cluster origins will lead to insights into the developmental and evolutionary significance of Hox gene clusters in vertebrate phylogeny and to their role in the origins of various vertebrate body plans. We have isolated two Hox clusters from the horn shark, Heterodontus francisci. These have been sequenced and compared with one another and with other chordate Hox clusters. The results show that one of the horn shark clusters (HoxM) is orthologous to the mammalian HoxA cluster and shows a structural similarity to the amphioxus cluster, whereas the other shark cluster (HoxN) is orthologous to the mammalian HoxD cluster based on cluster organization and a comparison with noncoding and Hox gene-coding sequences. The persistence of an identifiable HoxA cluster over an 800-million-year divergence time demonstrates that the Hox gene clusters are highly integrated and structured genetic entities. The data presented herein identify many noncoding sequence motifs conserved over 800 million years that may function as genetic control motifs essential to the developmental process.

Characterization of MADS homeotic genes in the fern Ceratopteris richardii

The MADS genes encode a family of transcription factors, some of which control the identities of floral organs in flowering plants. To understand the role of MADS genes in the evolution of floral organs, five MADS genes (CMADS1, 2, 3, 4, and 6) were cloned from the fern Ceratopteris richardii, a nonflowering plant. A gene tree of partial amino acid sequences of seed plant and fern MADS genes showed that the fern genes form three subfamilies. All members of one of the fern MADS subfamilies have additional amino-terminal amino acids, which is a synapomorphic character of the AGAMOUS subfamily of the flowering plant MADS genes. Their structural similarity indicates a sister relationship between the two subfamilies. The temporal and spatial patterns of expression of the five fern MADS genes were assessed by Northern blot analyses and in situ hybridizations. CMADS1, 2, 3, and 4 are expressed similarly in the meristematic regions and primordia of sporophyte shoots and roots, as well as in reproductive structures, including sporophylls and sporangial initials, although the amount of expression in each tissue is different in each gene. CMADS6 is expressed in gametophytic tissues but not in sporophytic tissues. The lack of organ-specific expression of MADS genes in the reproductive structures of the fern sporophyte may indicate that the restriction of MADS gene expression to specific reproductive organs and the specialization of MADS gene functions as homeotic selector genes in the flowering plant lineage were important in floral organ evolution.

FokI dimerization is required for DNA cleavage

FokI is a type IIs restriction endonuclease comprised of a DNA recognition domain and a catalytic domain. The structural similarity of the FokI catalytic domain to the type II restriction endonuclease BamHI monomer suggested that the FokI catalytic domains may dimerize. In addition, the FokI structure, presented in an accompanying paper in this issue of Proceedings, reveals a dimerization interface between catalytic domains. We provide evidence here that FokI catalytic domain must dimerize for DNA cleavage to occur. First, we show that the rate of DNA cleavage catalyzed by various concentrations of FokI are not directly proportional to the protein concentration, suggesting a cooperative effect for DNA cleavage. Second, we constructed a FokI variant, FokN13Y, which is unable to bind the FokI recognition sequence but when mixed with wild-type FokI increases the rate of DNA cleavage. Additionally, the FokI catalytic domain that lacks the DNA binding domain was shown to increase the rate of wild-type FokI cleavage of DNA. We also constructed an FokI variant, FokD483A, R487A, which should be defective for dimerization because the altered residues reside at the putative dimerization interface. Consistent with the FokI dimerization model, the variant FokD483A, R487A revealed greatly impaired DNA cleavage. Based on our work and previous reports, we discuss a pathway of DNA binding, dimerization, and cleavage by FokI endonuclease.

Interaction of voltage-gated sodium channels with the extracellular matrix molecules tenascin-C and tenascin-R

The type IIA rat brain sodium channel is composed of three subunits: a large pore-forming α subunit and two smaller auxiliary subunits, β1 and β2. The β subunits are single membrane-spanning glycoproteins with one Ig-like motif in their extracellular domains. The Ig motif of the β2 subunit has close structural similarity to one of the six Ig motifs in the extracellular domain of the cell adhesion molecule contactin (also called F3 or F11), which binds to the extracellular matrix molecules tenascin-C and tenascin-R. We investigated the binding of the purified sodium channel and the extracellular domain of the β2 subunit to tenascin-C and tenascin-R in vitro. Incubation of purified sodium channels on microtiter plates coated with tenascin-C revealed saturable and specific binding with an apparent Kd of ≈15 nM. Glutathione S-transferase-tagged fusion proteins containing various segments of tenascin-C and tenascin-R were purified, digested with thrombin to remove the epitope tag, immobilized on microtiter dishes, and tested for their ability to bind purified sodium channel or the epitope-tagged extracellular domain of β2 subunits. Both purified sodium channels and the extracellular domain of the β2 subunit bound specifically to fibronectin type III repeats 1–2, A, B, and 6–8 of tenascin-C and fibronectin type III repeats 1–2 and 6–8 of tenascin-R but not to the epidermal growth factor-like domain or the fibrinogen-like domain of these molecules. The binding of neuronal sodium channels to extracellular matrix molecules such as tenascin-C and tenascin-R may play a crucial role in localizing sodium channels in high density at axon initial segments and nodes of Ranvier or in regulating the activity of immobilized sodium channels in these locations.

Resveratrol, a polyphenolic compound found in grapes and wine, is an agonist for the estrogen receptor

The phytochemical resveratrol, which is found in grapes and wine, has been reported to have a variety of anti-inflammatory, anti-platelet, and anti-carcinogenic effects. Based on its structural similarity to diethylstilbestrol, a synthetic estrogen, we examined whether resveratrol might be a phytoestrogen. At concentrations (≈3–10 μM) comparable to those required for its other biological effects, resveratrol inhibited the binding of labeled estradiol to the estrogen receptor and it activated transcription of estrogen-responsive reporter genes transfected into human breast cancer cells. This transcriptional activation was estrogen receptor-dependent, required an estrogen response element in the reporter gene, and was inhibited by specific estrogen antagonists. In some cell types (e.g., MCF-7 cells), resveratrol functioned as a superagonist (i.e., produced a greater maximal transcriptional response than estradiol) whereas in others it produced activation equal to or less than that of estradiol. Resveratrol also increased the expression of native estrogen-regulated genes, and it stimulated the proliferation of estrogen-dependent T47D breast cancer cells. We conclude that resveratrol is a phytoestrogen and that it exhibits variable degrees of estrogen receptor agonism in different test systems. The estrogenic actions of resveratrol broaden the spectrum of its biological actions and may be relevant to the reported cardiovascular benefits of drinking wine.

PDB-REPRDB: a database of representative protein chains from the Protein Data Bank (PDB)

PDB-REPRDB is a database of representative protein chains from the Protein Data Bank (PDB). The previous version of PDB-REPRDB provided 48 representative sets, whose similarity criteria were predetermined, on the WWW. The current version is designed so that the user may obtain a quick selection of representative chains from PDB. The selection of representative chains can be dynamically configured according to the user’s requirement. The WWW interface provides a large degree of freedom in setting parameters, such as cut-off scores of sequence and structural similarity. One can obtain a representative list and classification data of protein chains from the system. The current database includes 20 457 protein chains from PDB entries (August 6, 2000). The system for PDB-REPRDB is available at the Parallel Protein Information Analysis system (PAPIA) WWW server (http://www.rwcp.or.jp/papia/).

Characterization of Two Novel Type I Ribosome-Inactivating Proteins from the Storage Roots of the Andean Crop Mirabilis expansa1

Two novel type I ribosome-inactivating proteins (RIPs) were found in the storage roots of Mirabilis expansa, an underutilized Andean root crop. The two RIPs, named ME1 and ME2, were purified to homogeneity by ammonium sulfate precipitation, cation-exchange perfusion chromatography, and C4 reverse-phase chromatography. The two proteins were found to be similar in size (27 and 27.5 kD) by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and their isoelectric points were determined to be greater than pH 10.0. Amino acid N-terminal sequencing revealed that both ME1 and ME2 had conserved residues characteristic of RIPs. Amino acid composition and western-blot analysis further suggested a structural similarity between ME1 and ME2. ME2 showed high similarity to the Mirabilis jalapa antiviral protein, a type I RIP. Depurination of yeast 26S rRNA by ME1 and ME2 demonstrated their ribosome-inactivating activity. Because these two proteins were isolated from roots, their antimicrobial activity was tested against root-rot microorganisms, among others. ME1 and ME2 were active against several fungi, including Pythium irregulare, Fusarium oxysporum solani, Alternaria solani, Trichoderma reesei, and Trichoderma harzianum, and an additive antifungal effect of ME1 and ME2 was observed. Antibacterial activity of both ME1 and ME2 was observed against Pseudomonas syringae, Agrobacterium tumefaciens, Agrobacterium radiobacter, and others.