Ocular cicatricial pemphigoid antigen: Partial sequence and biochemical characterization

Ocular cicatricial pemphigoid (OCP) is an autoimmune disease that affects mainly conjunctiva and other squamous epithelia. OCP is histologically characterized by a separation of the epithelium from underlying tissues within the basement membrane zone. Immunopathological studies demonstrate the deposition of anti-basement membrane zone autoantibodies in vivo. Purified IgG from sera of patients with active OCP identified a cDNA clone from a human keratinocyte cDNA library that had complete homology with the cytoplasmic domain of β4-integrin. The sera recognized a 205-kDa protein in human epidermal, human conjunctiva, and tumor cell lysates that was identified as β4-integrin by its reaction with polyclonal and monoclonal antibodies to human β4-integrin. Sera from patients with bullous pemphigoid, pemphigus vulgaris, and cicatricial pemphigoid-like diseases did not recognize the 205-kDa protein, indicating the specificity of the binding. These data strongly implicate a role for human β4-integrin in the pathogenesis of OCP. It should be emphasized that multiple antigens in the basement membrane zone of squamous epithelia may serve as targets for a wide spectrum of autoantibodies observed in vesiculobullous diseases. Molecular definition of these autoantigens will facilitate the classification and characterization of subsets of cicatricial pemphigoid and help distinguishing them from bullous pemphigoid. This study highlights the function and importance of β4-integrin in maintaining the attachment of epithelial cells to the basement membrane.

Structural aspects of activation pathways of aspartic protease zymogens and viral 3C protease precursors

The three-dimensional structures of the inactive protein precursors (zymogens) of the serine, cysteine, aspartic, and metalloprotease classes of proteolytic enzymes are known. Comparisons of these structures with those of the mature, active proteases reveal that, in general, the preformed, active conformations of the residues involved in catalysis are rendered sterically inaccessible to substrates by the residues of the zymogens’ N-terminal extensions or prosegments. The prosegments interact in nonsubstrate-like fashions with the residues of the active sites in most of the cases. The gastric aspartic proteases have a well-characterized zymogen conversion pathway. Structures of human progastricsin, the inactive intermediate 2, and active human pepsin are known and have been used to define the conversion pathway. The structure of the zymogen precursor of plasmepsin II, the malarial aspartic protease, shows a new twist on the mode of inactivation used by the gastric zymogens. The prosegment of proplasmepsin disrupts the active conformation of the two catalytic aspartic acid residues by inducing a major reorientation of the two domains of the mature protease. The picornaviral 2A and 3C proteases have a chymotrypsin-like tertiary structure but with a cysteine nucleophile. These enzymes cleave themselves from the viral polyprotein in cis (intramolecular cleavage) and carry out trans cleavages of other scissile peptides important for the virus life cycle. Although the structure of the precursor viral polyprotein is unknown, it probably resembles the organization of the proenzymes of the bacterial serine proteases, subtilisin, and α-lytic protease. Cleavage of the prosegment is known to occur in cis for these precursor molecules.

Induction of primordial germ cells from murine epiblasts by synergistic action of BMP4 and BMP8B signaling pathways

Extraembryonic ectoderm-derived factors instruct the pluripotent epiblast cells to develop toward a restricted primordial germ cell (PGC) fate during murine gastrulation. Genes encoding Bmp4 of the Dpp class and Bmp8b of the 60A class are expressed in the extraembryonic ectoderm and targeted mutation of either results in severe defects in PGC formation. It has been shown that heterodimers of DPP and 60A classes of bone morphogenetic proteins (BMPs) are more potent than each homodimers in bone and mesoderm induction in vitro, suggesting that BMP4 and BMP8B may form heterodimers to induce PGCs. To investigate how BMP4 and BMP8B interact and signal for PGC induction, we cocultured epiblasts of embryonic day 6.0–6.25 embryos with BMP4 and BMP8B proteins produced by COS cells. Our data show that BMP4 or BMP8B homodimers alone cannot induce PGCs whereas they can in combination, providing evidence that two BMP pathways are simultaneously required for the generation of a given cell type in mammals and also providing a prototype method for PGC induction in vitro. Furthermore, the PGC defects of Bmp8b mutants can be rescued by BMP8B homodimers whereas BMP4 homodimers cannot mitigate the PGC defects of Bmp4 null mutants, suggesting that BMP4 proteins are also required for epiblast cells to gain germ-line competency before the synergistic action of BMP4 and BMP8B.

Chloroplast DNA evidence of colonization, adaptive radiation, and hybridization in the evolution of the Macaronesian flora.

Most evolutionary studies of oceanic islands have focused on the Pacific Ocean. There are very few examples from the Atlantic archipelagos, especially Macaronesia, despite their unusual combination of features, including a close proximity to the continent, a broad range of geological ages, and a biota linked to a source area that existed in the Mediterranean basin before the late Tertiary. A chloroplast DNA (cpDNA) restriction site analysis of Argyranthemum (Asteraceae: Anthemideae), the largest endemic genus of plants of any volcanic archipelago in the Atlantic Ocean, was performed to examine patterns of plant evolution in Macaronesia. cpDNA data indicated that Argyranthemum is a monophyletic group that has speciated recently. The cpDNA tree showed a weak correlation with the current sectional classification and insular distribution. Two major cpDNA lineages were identified. One was restricted to northern archipelagos--e.g., Madeira, Desertas, and Selvagens--and the second comprised taxa endemic to the southern archipelago--e.g., the Canary Islands. The two major radiations identified in the Canaries are correlated with distinct ecological habitats; one is restricted to ecological zones under the influence of the northeastern trade winds and the other to regions that are not affected by these winds. The patterns of phylogenetic relationships in Argyranthemum indicate that interisland colonization between similar ecological zones is the main mechanism for establishing founder populations. This phenomenon, combined with rapid radiation into distinct ecological zones and interspecific hybridization, is the primary explanation for species diversification.

Life-span, T-cell responses, and incidence of lymphomas in congenic mice.

Survival, T-cell functions, and postmortem histopathology were studied in H-2 congenic strains of mice bearing H-2b, H-2k, and H-2d haplotypes. Males lived longer than females in all homozygous and heterozygous combinations except for H-2d homozygotes, which showed no differences between males and females. Association of heterozygosity with longer survival was observed only with H-2b/H-2b and H-2b/H-2d mice. Analysis using classification and regression trees (CART) showed that both males and females of H-2b homozygous and H-2k/H-2b mice had the shortest life-span of the strains studied. In histopathological analyses, lymphomas were noted to be more frequent in females, while hemangiosarcomas and hepatomas were more frequent in males. Lymphomas appeared earlier than hepatomas or hemangiosarcomas. The incidence of lymphomas was associated with the H-2 haplotype--e.g., H-2b homozygous mice had more lymphomas than did mice of the H-2d haplotype. More vigorous T-cell function was maintained with age (27 months) in H-2d, H-2b/H-2d, and H-2d/H-2k mice as compared with H-2b, H-2k, and H-2b/H-2k mice, which showed a decline of T-cell responses with age.

Towards a unified framework for opinion retrieval, mining and summarization

The exponential increase of subjective, user-generated content since the birth of the Social Web, has led to the necessity of developing automatic text processing systems able to extract, process and present relevant knowledge. In this paper, we tackle the Opinion Retrieval, Mining and Summarization task, by proposing a unified framework, composed of three crucial components (information retrieval, opinion mining and text summarization) that allow the retrieval, classification and summarization of subjective information. An extensive analysis is conducted, where different configurations of the framework are suggested and analyzed, in order to determine which is the best one, and under which conditions. The evaluation carried out and the results obtained show the appropriateness of the individual components, as well as the framework as a whole. By achieving an improvement over 10% compared to the state-of-the-art approaches in the context of blogs, we can conclude that subjective text can be efficiently dealt with by means of our proposed framework.

A novel information theory method for filter feature selection

In this paper, we propose a novel filter for feature selection. Such filter relies on the estimation of the mutual information between features and classes. We bypass the estimation of the probability density function with the aid of the entropic-graphs approximation of Rényi entropy, and the subsequent approximation of the Shannon one. The complexity of such bypassing process does not depend on the number of dimensions but on the number of patterns/samples, and thus the curse of dimensionality is circumvented. We show that it is then possible to outperform a greedy algorithm based on the maximal relevance and minimal redundancy criterion. We successfully test our method both in the contexts of image classification and microarray data classification.

Nueva técnica de fusión de clasificadores aplicada a la mejora de la segmentación de audio

Este artículo presenta un nuevo algoritmo de fusión de clasificadores a partir de su matriz de confusión de la que se extraen los valores de precisión (precision) y cobertura (recall) de cada uno de ellos. Los únicos datos requeridos para poder aplicar este nuevo método de fusión son las clases o etiquetas asignadas por cada uno de los sistemas y las clases de referencia en la parte de desarrollo de la base de datos. Se describe el algoritmo propuesto y se recogen los resultados obtenidos en la combinación de las salidas de dos sistemas participantes en la campaña de evaluación de segmentación de audio Albayzin 2012. Se ha comprobado la robustez del algoritmo, obteniendo una reducción relativa del error de segmentación del 6.28% utilizando para realizar la fusión el sistema con menor y mayor tasa de error de los presentados a la evaluación.

A massive association around the obscured open cluster RSGC3

Context. Four clusters of red supergiants have been discovered in a region of the Milky Way close to base of the Scutum-Crux Arm and the tip of the Long Bar. Population synthesis models indicate that they must be very massive to harbour so many supergiants. If the clusters are physically connected, this Scutum Complex would be the largest and most massive star-forming region ever identified in the Milky Way. Aims. The spatial extent of one of these clusters, RSGC3, has not been investigated. In this paper we explore the possibility that a population of red supergiants could be located in its vicinity. Methods. We utilised 2MASS JHKS photometry to identify candidate obscured luminous red stars in the vicinity of RSGC3. We observed a sample of candidates with the TWIN spectrograph on the 3.5-m telescope at Calar Alto, obtaining intermediate-resolution spectroscopy in the 8000−9000 Å range. We re-evaluated a number of classification criteria proposed in the literature for this spectral range and found that we could use our spectra to derive spectral types and luminosity classes. Results. We measured the radial velocity of five members of RSGC3, finding velocities similar to the average for members of Stephenson 2. Among the candidates observed outside the cluster, our spectra revealed eight M-type supergiants at distances <18′ from the centre of RSGC3, distributed in two clumps. The southern clump is most likely another cluster of red supergiants, with reddening and age identical to RSGC3. From 2MASS photometry, we identified four likely supergiant members of the cluster in addition to the five spectroscopically observed. The northern clump may be a small cluster with similar parameters. Photometric analysis of the area around RSGC3 suggests the presence of a large (>30) population of red supergiants with similar colours. Conclusions. Our data suggest that the massive cluster RSGC3 is surrounded by an extended association, which may be very massive ( ≳ 105 M⊙). We also show that supergiants in the Scutum Complex may be characterised via a combination of 2MASS photometry and intermediate-to-high-resolution spectroscopy in the Z band.

Sentiment classification for early detection of health alerts in the chemical textile domain

In the chemical textile domain experts have to analyse chemical components and substances that might be harmful for their usage in clothing and textiles. Part of this analysis is performed searching opinions and reports people have expressed concerning these products in the Social Web. However, this type of information on the Internet is not as frequent for this domain as for others, so its detection and classification is difficult and time-consuming. Consequently, problems associated to the use of chemical substances in textiles may not be detected early enough, and could lead to health problems, such as allergies or burns. In this paper, we propose a framework able to detect, retrieve, and classify subjective sentences related to the chemical textile domain, that could be integrated into a wider health surveillance system. We also describe the creation of several datasets with opinions from this domain, the experiments performed using machine learning techniques and different lexical resources such as WordNet, and the evaluation focusing on the sentiment classification, and complaint detection (i.e., negativity). Despite the challenges involved in this domain, our approach obtains promising results with an F-score of 65% for polarity classification and 82% for complaint detection.

Epithelial Ovarian Cancers and Endometriosis

Aims: To determine the prevalence of endometriosis in epithelial ovarian cancers (EOC) and the association among their histological subtypes and with endometrial carcinoma. Methods: An observational cohort study performed in 192 patients operated on for EOC, 30 women with atypical endometriosis and 17 with p53 positive endometriosis. Data on associated endometriosis and endometrial carcinomas, histological subtypes, tumor stage, clinical and pathological characteristics and survival were analyzed. Results: Twenty cases of EOC (10.4%) had also endometriosis (12.7 in borderline and 9.3% in invasive cases), being a synchronous finding in most cases. Endometriosis associated with serous or mucinous EOC was observed in 2.2 and 2.7% of cases, respectively. However, this association was observed in 50 of endometrioid and 23% of clear cell EOC. Age, parity and tumor stage were lower in endometriosis-associated EOC patients; and all associated cases were type I (Kurman and Shih's classification) and showed better results in survival rate. Endometrial carcinoma was more frequently associated with endometrioid EOC (25%). Conclusions: There is a significant association between endometriosis, including atypical forms, and endometrioid and clear cell carcinomas, but not with other EOC histotypes. The presence of endometriosis in EOC suggests a better prognosis and an intermediate stage within the progression endometriosis-carcinoma.

The Services Dimension of TTIP. Paper No. 6 in the CEPS-CTR project “TTIP in the Balance’’ and CEPS Special Report No. 106, 8 May 2015

This CEPS Special Report examines the main facets of the debate about TTIP and services. First, it looks at the political and economic context and the various alternatives in terms of political support, stressing that only a partnership that ensures substantial economic gains will attract the support of the top policy-makers. Second, the paper makes the point that large economic gains in services require deep discussions on regulatory issues, and third, such discussions cannot rely on the negotiating techniques normally used for goods. There is thus a need to adopt a new approach, based on the mutual recognition and equivalence of regulations enforced in the services concerned, preceded by a mutual evaluation to grant such equivalence – all measures to be carried out by the regulatory bodies concerned, not by trade negotiators. This new game is a complex one but it has huge side benefits: it induces each TTIP partner to review the quality of their own regulations; it is at ease with the notion of a ‘living’ (evolving) agreement; and it can easily be open to third countries. All these benefits should reassure a general public that is fearful of a hastily baked deal.

2nd, 3rd, 4th and 5th interim reports ...

Mode of access: Internet.

A scripture catechism, for the instruction of children and servants /

Includes publisher's advertisement on lower cover.

A guide to the Mental deficiency act, 1913 : containing a legal and general exposition of the act, with suggestions to local authorities, managers and others for the organization and administration of the work dealing with the mental defective /

Mode of access: Internet.