Showing papers by "University of Oviedo published in 2004"
Richard A. Gibbs1, George M. Weinstock1, Michael L. Metzker1, Donna M. Muzny1 +239 more•Institutions (35)
TL;DR: This first comprehensive analysis of the genome sequence of the Brown Norway (BN) rat strain is reported, which is the third complete mammalian genome to be deciphered, and three-way comparisons with the human and mouse genomes resolve details of mammalian evolution.
Abstract: The laboratory rat (Rattus norvegicus) is an indispensable tool in experimental medicine and drug development, having made inestimable contributions to human health. We report here the genome sequence of the Brown Norway (BN) rat strain. The sequence represents a high-quality 'draft' covering over 90% of the genome. The BN rat sequence is the third complete mammalian genome to be deciphered, and three-way comparisons with the human and mouse genomes resolve details of mammalian evolution. This first comprehensive analysis includes genes and proteins and their relation to human disease, repeated sequences, comparative genome-wide studies of mammalian orthologous chromosomal regions and rearrangement breakpoints, reconstruction of ancestral karyotypes and the events leading to existing species, rates of variation, and lineage-specific and lineage-independent evolutionary events such as expansion of gene families, orthology relations and protein evolution.
1,964 citations
TL;DR: In this paper, a quasi-harmonic Debye model is used to generate the Debye temperature Θ(V), obtains the non-equilibrium Gibbs function G★(V;p,T), and minimizes G★ to derive the thermal equation of state (EOS) V(p, T) and the chemical potential G(p and T) of the corresponding phase.
1,480 citations
TL;DR: A better understanding of the functional complexity of this proteolytic system and global approaches to identify the relevant MMPs which must be targeted in each individual cancer patient, will be necessary to clarify whether MMP inhibition may be part of future therapies against cancer.
Abstract: Over the last years, the relevance of the matrix metalloproteinase (MMP) family in cancer research has grown considerably. These enzymes were initially associated with the invasive properties of tumour cells, owing to their ability to degrade all major protein components of the extracellular matrix (ECM) and basement membranes. However, further studies have demonstrated the implication of MMPs in early steps of tumour evolution, including stimulation of cell proliferation and modulation of angiogenesis. The establishment of causal relationships between MMP overproduction in tumour or stromal cells and cancer progression has prompted the development of clinical trials with a series of inhibitors designed to block the proteolytic activity of these enzymes. Unfortunately, the results derived from using broad-spectrum MMP inhibitors (MMPIs) for treating patients with advanced cancer have been disappointing in most cases. There are several putative explanations for the lack of success of these MMPIs including the recent finding that some MMPs may play a paradoxical protective role in tumour progression. These observations together with the identification of novel functions for MMPs in early stages of cancer have made necessary a reformulation of MMP inhibition strategies. A better understanding of the functional complexity of this proteolytic system and global approaches to identify the relevant MMPs which must be targeted in each individual cancer patient, will be necessary to clarify whether MMP inhibition may be part of future therapies against cancer.
595 citations
TL;DR: It is found that fibroblasts and cancer cells express an indistinguishable pericellular collagenolytic activity that allows them to traverse the ECM and that MT1-MMP serves as the major cell-associated proteinase necessary to confer normal or neoplastic cells with invasive activity.
Abstract: As cancer cells traverse collagen-rich extracellular matrix (ECM) barriers and intravasate, they adopt a fibroblast-like phenotype and engage undefined proteolytic cascades that mediate invasive activity. Herein, we find that fibroblasts and cancer cells express an indistinguishable pericellular collagenolytic activity that allows them to traverse the ECM. Using fibroblasts isolated from gene-targeted mice, a matrix metalloproteinase (MMP)–dependent activity is identified that drives invasion independently of plasminogen, the gelatinase A/TIMP-2 axis, gelatinase B, collagenase-3, collagenase-2, or stromelysin-1. In contrast, deleting or suppressing expression of the membrane-tethered MMP, MT1-MMP, in fibroblasts or tumor cells results in a loss of collagenolytic and invasive activity in vitro or in vivo. Thus, MT1-MMP serves as the major cell-associated proteinase necessary to confer normal or neoplastic cells with invasive activity.
585 citations
TL;DR: In this paper, the authors discuss the virtues and drawbacks of different hypotheses about basic carbon sites in view of experimental and theoretical results and discuss the importance of basic sites on carbon surfaces.
466 citations
TL;DR: The results show that collaborative culture encourages the development of organizational learning, which at the same time, has a significant effect on business performance, and empirical evidence for the hypothesis that collaborativeculture influences organizational learning which in turn influences business performance is provided.
Abstract: Aims to analyze how the organizational culture impacts knowledge management, organizational learning and ultimately the performance of the firm. The degree to which collaborative culture influences organizational learning and performance is investigated for 195 Spanish firms. The technique used was structural equation modeling (SEM). The results show, first of all, that collaborative culture encourages the development of organizational learning, which at the same time, has a significant effect on business performance. And, second, it is highlighted that collaborative culture does not constitute in itself a source of competitive advantages. Collaborative culture must modify, through learning, the organization’s guidelines and attitudes in order to improve competitive performance. Perhaps the most significant limitation of the study is associated with the use of cross‐sectional data. While we presented and tested models in which we assumed a causal flow from collaborative culture to organizational learning to organizational performance, there is the possibility that these relationships may occur in reverse order. In future researches it would be interesting to analyze the influence that other variables, such organizational structure, leadership and corporate strategy have on learning. The establishment of a knowledge strategy can be determined by a global approach, which affects all fields in organization. For knowledge management initiatives to be truly effective must take into account the social contexts in which learning take place. Culture need to be re‐examined in light of its role in managing the overall organizational learning infrastructure. This study provides empirical evidence for the hypothesis that collaborative culture influences organizational learning which in turn influences business performance. The current study provides some understanding of the manner in which collaborative culture influence organizational outcomes.
432 citations
TL;DR: In this article, a latent class stochastic frontier model is proposed to estimate the efficiency of Spanish banking data. But the model assumes that the underlying production technology is the same for all firms.
Abstract: Efficiency estimation in stochastic frontier models typically assumes that the underlying production technology is the same for all firms. There might, however, be unobserved differences in technologies that might be inappropriately labeled as inefficiency if such variations in technology are not taken into account. We address this issue by estimating a latent class stochastic frontier model in a panel data framework. An application of the model is presented using Spanish banking data. Our results show that bank-heterogeneity can be fully controlled when a model with four classes is estimated.
360 citations
TL;DR: In this article, a review examines the literature on non-covalent MIP-based electrochemical sensors over the last 10 years, with insight into the different sensing phases, electrochemical transductions and integration strategies.
Abstract: Molecularly imprinted polymers (MIPs) are becoming an important class of synthetic materials mimicking molecular recognition by natural receptors. This review examines the literature on non-covalent MIP-based electrochemical sensors over the last 10 years. With insight into the different sensing phases, electrochemical transductions and integration strategies, we evaluate achievements and difficulties to date and assess future prospects.
325 citations
TL;DR: TIMP-resistant, active MMP-8 expressed on the surface of activated PMN is likely to be an important form of M MP-8, regulating lung inflammation and collagen turnover in vivo.
Abstract: Little is known about the cell biology or the biologic roles of polymorphonuclear cell (PMN)-derived matrix metalloproteinase-8 (MMP-8). When activated with proinflammatory mediators, human PMN release only approximately 15-20% of their content of MMP-8 ( approximately 60 ng/10(6) cells) exclusively as latent pro-MMP-8. However, activated PMN incubated on type I collagen are associated with pericellular collagenase activity even when bathed in serum. PMN pericellular collagenase activity is attributable to membrane-bound MMP-8 because: 1) MMP-8 is expressed in an inducible manner in both pro- and active forms on the surface of human PMN; 2) studies of activated PMN from mice genetically deficient in MMP-8 (MMP-8(-/-)) vs wild-type (WT) mice show that membrane-bound MMP-8 accounts for 92% of the MMP-mediated, PMN surface type I collagenase activity; and 3) human membrane-bound MMP-8 on PMN cleaves types I and II collagens, and alpha(1)-proteinase inhibitor, but is substantially resistant to inhibition by tissue inhibitor of metalloproteinase-1 (TIMP-1) and TIMP-2. Binding of MMP-8 to the PMN surface promotes its stability because soluble MMP-8 has t(1/2) = 7.5 h at 37 degrees C, but membrane-bound MMP-8 retains >80% of its activity after incubation at 37 degrees C for 18 h. Studies of MMP-8(-/-) vs WT mice given intratracheal LPS demonstrate that 24 h after intratracheal LPS, MMP-8(-/-) mice have 2-fold greater accumulation of PMN in the alveolar space than WT mice. Thus, MMP-8 has an unexpected, anti-inflammatory role during acute lung injury in mice. TIMP-resistant, active MMP-8 expressed on the surface of activated PMN is likely to be an important form of MMP-8, regulating lung inflammation and collagen turnover in vivo.
249 citations
TL;DR: The physiological and pathological roles of autophagy, as well as the molecular mechanisms underlying this multifunctional pathway, are discussed in this review.
Abstract: Autophagy is a degradative mechanism mainly involved in the recycling and turnover of cytoplasmic constituents from eukaryotic cells. Over the last years, yeast genetic screens have considerably increased our knowledge about the molecular mechanisms of autophagy, and a number of genes involved in fundamental steps of the autophagic pathway have been identified. Most of these autophagy genes are present in higher eukaryotes indicating that this process has been evolutionarily conserved. In yeast, autophagy is mainly involved in adaptation to starvation, but in multicellular organisms this route has emerged as a multifunctional pathway involved in a variety of additional processes such as programmed cell death, removal of damaged organelles and development of different tissue-specific functions. Furthermore, autophagy is associated with a growing number of pathological conditions, including cancer, myopathies and neurodegenerative disorders. The physiological and pathological roles of autophagy, as well as the molecular mechanisms underlying this multifunctional pathway, are discussed in this review.
238 citations
TL;DR: In this article, the relationship between technical efficiency and size might be affected by farm heterogeneity, and a set of control variables are chosen using a production model where technical efficiency is introduced as a parameter.
TL;DR: The utilization bound for earliest deadline first EDF scheduling is extended from uniprocessors to homogeneous multiprocessor systems with partitioning strategies, and the basic task model is extended to include resource sharing, release jitter, deadlines less than periods, aperiodic tasks, non-preemptive sections, context switches, and mode changes.
Abstract: The utilization bound for earliest deadline first (EDF) scheduling is extended from uniprocessors to homogeneous multiprocessor systems with partitioning strategies. First results are provided for a basic task model, which includes periodic and independent tasks with deadlines equal to periods. Since the multiprocessor utilization bounds depend on the allocation algorithm, different allocation algorithms have been considered, ranging from simple heuristics to optimal allocation algorithms. As multiprocessor utilization bounds for EDF scheduling depend strongly on task sizes, all these bounds have been obtained as a function of a parameter which takes task sizes into account. Theoretically, the utilization bounds for multiprocessor EDF scheduling can be considered a partial solution to the bin-packing problem, which is known to be NP-complete. The basic task model is extended to include resource sharing, release jitter, deadlines less than periods, aperiodic tasks, non-preemptive sections, context switches, and mode changes.
TL;DR: Results provide additional evidence of the extreme complexity and diversity of the USP proteolytic system in human tissues and open the possibility to explore the relevance of their multiple components in the regulation of ubiquitin-mediated pathways in normal and pathological functions.
TL;DR: Comparisons of genomic analysis of rat protease inhibitors and the expansion of families of cysteine and serine protease inhibitor in rodents with respect to human may provide new views on the functional diversity of proteases and inhibitors and contribute to the development of innovative strategies for treating proteolysis diseases.
Abstract: Proteases perform important roles in multiple biological and pathological processes. The availability of the rat genome sequence has facilitated the analysis of the complete protease repertoire or degradome of this model organism. The rat degradome consists of at least 626 proteases and homologs, which are distributed into 24 aspartic, 160 cysteine, 192 metallo, 221 serine, and 29 threonine proteases. This distribution is similar to that of the mouse degradome but is more complex than that of the human degradome composed of 561 proteases and homologs. This increased complexity of rat proteases mainly derives from the expansion of several families, including placental cathepsins, testases, kallikreins, and hematopoietic serine proteases, involved in reproductive or immunological functions. These protease families have also evolved differently in rat and mouse and may contribute to explain some functional differences between these closely related species. Likewise, genomic analysis of rat protease inhibitors has shown some differences with mouse protease inhibitors and the expansion of families of cysteine and serine protease inhibitors in rodents with respect to human. These comparative analyses may provide new views on the functional diversity of proteases and inhibitors and contribute to the development of innovative strategies for treating proteolysis diseases.
TL;DR: In this article, the differences existing in the relations between bottling/packaging firms belonging to the food and drinks sector and their suppliers (fundamentally bottle/jar manufacturers) and their customers (end consumers of the packaged or bottled products) in two European countries with different characteristics were analyzed.
TL;DR: The objective of this project is the development of plant supervision techniques based on self-organizing map (SOM) for the implementation in a wastewater treatment plant by means of the Davies–Bouldin index.
TL;DR: In this paper, surface-modified CdSe semiconductor quantum dots (QDs), with nanoparticle size distribution in the order of 2-7nm, have been synthesized for optical determination of cyanide ions.
TL;DR: A new enzymatic process is described that widens the applicability of these biocatalysts in organic synthesis by catalyse Michael-type addition of secondary amines to acrylonitrile.
TL;DR: Results were obtained when treating with activated carbon, the leachate from the biological treatment plant at the La Zoreda landfill; in this case without decreasing the pH.
TL;DR: A method to compute two-electron integrals over arbitrary regions of space is introduced and particularized to the basins appearing in the quantum theory of atoms in molecules, showing that the approach is always convergent and computationally efficient.
Abstract: A method to compute two-electron integrals over arbitrary regions of space is introduced and particularized to the basins appearing in the quantum theory of atoms in molecules. The procedure generalizes the conventional multipolar approach to account for overlapping densities. We show that the approach is always convergent and computationally efficient, scaling as N4 in the worst, two-center case. Several numerical results supporting our claims are also presented.
TL;DR: Sequence analysis indicates that the macrolide ring of borrelidin is formed by a modular polyketide synthase (PKS) (borA1-A6), a result that was confirmed by disruption ofborA3.
TL;DR: It is reported that Hxk2 has a glucose-regulated nuclear localization and that Mig1, a transcriptional repressor responsible for glucose repression of many genes, is required to sequester HxK2 into the nucleus of S. cerevisiae during growth in glucose medium.
TL;DR: In this article, the authors propose a conceptual framework to analyze organizational learning and its outcomes, focusing on the strategy perspective of organizational learning with special attention to the resource and capabilities theory of the firm.
Abstract: This paper is structured into four sections. The first section proposes a conceptual framework to analyze organizational learning and its outcomes. It focuses on the strategy perspective of organizational learning – with special attention to the resource and capabilities theory of the firm – addressing its ontology, contributions and problematic. The second section is focused on a particular type of knowledge – the structural capital – that is institutionalized knowledge in the form of organizational processes, structures, technologies, policies and culture. In sum, it represents all forms of knowledge deposits that are not supported by the human being such as organizational routines, strategies and processes and is the result of learning at organizational level. This section studies the map of different types of organizational structural capital of companies: idiosyncratic, core, ancillary and compulsory. Section three shows the results of a case study done in pioneer learning organizations in Europe regarding knowledge measuring and reporting. It analyzes the main indicators used for quantifying the knowledge embedded in the organization and its processes. Finally, the last section explores the main results and implications for knowledge management drawn from this paper.
TL;DR: Findings clearly identify ANXA1 as an effective differentiation marker for the histopathological grading of HNSCCs and for the detection of epithelial dysplasia.
Abstract: Annexin A1 (ANXA1) protein expression was evaluated by Western blot in a series of 32 head and neck squamous cell carcinomas (HNSCCs) in a search for molecular alterations that could serve as useful diagnostic/prognostic markers. ANXA1 down-regulation was observed in 24 cases (75%) compared with patient-matched normal epithelium. In relation to clinicopathological variables, ANXA1 down-regulation was significantly associated with advanced T stages (P = 0.029), locoregional lymph node metastases (P = 0.038), advanced disease stage (P = 0.006), hypopharyngeal localization (P = 0.038), and poor histological differentiation (P = 0.005). ANXA1 expression was also analyzed by immunohistochemistry in paraffin-embedded sections from 22 of 32 HNSCCs and 8 premalignant lesions. All dysplastic tissues showed significantly reduced ANXA1 expression compared to a strong positive signal observed in adjacent normal epithelia (except basal and suprabasal cells). A close association was observed between ANXA1 expression and the histological grade in HNSCC. Well-differentiated tumors presented a positive ANXA1 signal in highly keratinized areas whereas moderately and poorly differentiated tumors exhibited very weak or negative staining. Our findings clearly identify ANXA1 as an effective differentiation marker for the histopathological grading of HNSCCs and for the detection of epithelial dysplasia.
TL;DR: In this article, the chemistry and catalytic applications of Group 8 half-sandwich complexes containing non-heteroatom stabilized α, β -unsaturated alkylidene and cumulenylidene groups are reported.
TL;DR: Evidence is presented that rodlet formation is conserved in the streptomycetes, and expression per aerial hypha was similar to that in the wild‐type strain, indicating that expression of the rdl genes is initiated after the hypha has sensed that it has grown into the air.
Abstract: Streptomycetes form hydrophobic aerial hyphae that eventually septate into hydrophobic spores. Both aerial hyphae and spores possess a typical surface layer called the rodlet layer. We present here evidence that rodlet formation is conserved in the streptomycetes. The formation of the rodlet layer is the result of the interplay between rodlins and chaplins. A strain of Streptomyces coelicolor in which the rodlin genes rdlA and/or rdlB were deleted no longer formed the rodlet layer. Instead, these surfaces were decorated with fine fibrils. Deletion of all eight chaplin genes (strain DeltachpABCDEFGH) resulted in the absence of the rodlet layer as well as the fibrils at surfaces of aerial hyphae and spores. Apart from coating these surfaces, chaplins are involved in the escape of hyphae into the air, as was shown by the strong reduction in the number of aerial hyphae in the DeltachpABCDEFGH strain. The decrease in the number of aerial hyphae correlated with a lower expression of the rdl genes in the colony. Yet, expression per aerial hypha was similar to that in the wild-type strain, indicating that expression of the rdl genes is initiated after the hypha has sensed that it has grown into the air.
TL;DR: Melatonin is a specific inhibitor of E2-induced ERα-mediated transcription in both estrogen response element- and AP1-containing promoters, whereas ERβ-mediated transactivation is not inhibited or even activated at certain promoters, suggesting a synergistic pharmacological effect of melatonin and current anti-estrogen drugs.
TL;DR: In this article, the authors studied the effect of the anomalous magnetic and electric dipole moments of the tau lepton in the DELPHI experiment at LEP2 during the years 1997 - 2000.
Abstract: Tau-pair production in the process e(+)e(-) --> e(+)e(-) tau(+)tau(-) was studied using data collected by the DELPHI experiment at LEP2 during the years 1997 - 2000. The corresponding integrated luminosity is 650 pb(-1). The values of the cross-section obtained are found to be in agreement with QED predictions. Limits on the anomalous magnetic and electric dipole moments of the tau lepton are deduced.
TL;DR: The results suggest that discordance among successive scales allows to link directly frugivory patterns to resource-tracking mechanisms acting at particular scales, resulting in more informative than concordance observational data, in which landscape patterns might result from accumulated effect of local mechanisms.
Abstract: Scaling is relevant for the analysis of plant-frugivore interaction, since the ecological and evolutionary outcomes of seed dispersal depend on the spatial and temporal scale at which frugivory patterns emerge. We analyse the relationship between fruit abundance and frugivore activity at local and landscape spatial scales in two different systems composed, respectively, by the bird-dispersed woody plants Juniperus communis and Bursera fagaroides, and their frugivore assemblages. We use a hierarchical approach of nested patchiness of fruit-resource, where patches are defined by individual plants within site, at the local scale, and by sites within region, at the landscape scale. The structure of patches is also described in terms of contrast (differences in fruit availability among patches) and aggregation (spatial distribution of patches). For J. communis, frugivore activity was positively related to fruit availability at the landscape scale, this pattern seldom emerging at the local scale; conversely, B. fagaroides showed a general trend of positive local pattern that disappeared at the landscape scale. These particular trends might be partially explained by differences in contrast and aggregation. The strong contrast among plants within site together with a high aggregation among sites would promote the B. fagaroides pattern to be only local, whereas in J. communis, low aggregation among sites within region would favour a sharp landscape-scale pattern. Both systems showed discordant patterns of fruitresource tracking among consecutive spatial scales, but the sense of discordance differed among systems. These results, and the available multi-scale frugivory data, suggest that discordance among successive scales allows to link directly frugivory patterns to resource-tracking mechanisms acting at particular scales, resulting, thus, more informative than concordance observational data, in which landscape patterns might result from accumulated effect of local mechanisms. In this context, we propose new methodological approaches for a better understanding of the hierarchical behavioural mechanisms underpinning the multi-scale resource tracking by frugivores.