Economic and social activities are undergoing radical changes, which can be labelled as 'knowledge economy and/or society'. In this sense, intellectual capital (IC), or knowledge assets, as the ...fourth factor of production, is replacing the other ones-job, land and capital. This article tries to offer the origins and nature of the firm's IC that can be labelled as 'An Intellectual Capital-Based View of the Firm Competition'. This framework tries to highlight the strategic role of different intangible assets like talented and committed workers, cultural values, or long-term relationships among the firm and its stakeholders-customers, allies, suppliers and society in general - in gaining and sustaining competitive advantages, being the management of IC a key issue in the management agenda.
Developing successful technological innovations is essential for creating and sustaining a firm's competitive advantage. This paper analyses the internal complexity that characterises technological ...innovation in firms. The innovation capability of a firm depends closely on its intellectual and/or organisational knowledge assets and on its ability to deploy these assets. This paper goes beyond the direct relationships between human and technological knowledge assets and product innovation, proposing a moderating role of innovation culture on these relationships. Using a questionnaire to survey 251 Spanish high and medium-high technological manufacturing firms, multiple regression models were developed. After analysing the relationship between human capital and product innovation developed by firms, the results reveal the existence of the moderating role of innovation culture in a knowledge-based product innovation model.
► We analyse the role of firms' intellectual capital on product innovation. ►We test our direct and moderating propositions on 251 Spanish high-tech firms. ►Human capital, technological knowledge assets and innovation culture have a direct effect. ►Innovation culture positively moderates the effect of human capital.
: Melatonin (N‐acetyl‐5‐methoxytryptamine) is a tryptophan‐derived signal with important physiological roles in mammals. Although the presence of melatonin in plants may be universal, its endogenous ...function in plant tissues is unknown. On the basis of its structural similarity to indole‐3‐acetic acid, recent studies mainly focusing on root growth in several plant species have suggested a potential auxin‐like activity of melatonin. However, direct evidence about the mechanisms of action of this regulator is lacking. In this work, we used Arabidopsis thaliana seedlings as a model system to evaluate the effects of melatonin on plant growth and development. Melatonin modulated root system architecture by stimulating lateral and adventitious root formation but minimally affected primary root growth or root hair development. The auxin activity of melatonin in roots was investigated using the auxin‐responsive marker constructs DR5:uidA, BA3:uidA, and HS::AXR3NT‐GUS. Our results show that melatonin neither activates auxin‐inducible gene expression nor induces the degradation of HS::AXR3NT‐GUS, indicating that root developmental changes elicited by melatonin were independent of auxin signaling. Taken together, our results suggest that melatonin is beneficial to plants by increasing root branching and that root development processes elicited by this novel plant signal are likely independent of auxin responses.
Objective
To characterize the alterations, as well as their mechanisms, induced in the HLA–B27–bound peptidome expressed in live cells by the natural ERAP1 polymorphisms predisposing to ankylosing ...spondylitis (AS): R528K and N575D/Q725R.
Methods
HLA–B*27:05–bound peptides were isolated from 3 human lymphoid cell lines expressing distinct ERAP1 variants differing at residues 528 and/or 575/725. The high‐performance liquid chromatography–fractionated peptide pools were compared by mass spectrometry based on identity of molecular mass and chromatographic retention time. The relative amount of each shared peptide in any given cell line pair was estimated from the respective ion peak intensities. Peptide sequencing was also carried out by mass spectrometry.
Results
HLA–B27–bound ligands predominant in the context of the ERAP1 variant with K528 collectively showed higher molecular mass, higher frequency of N‐terminal residues resistant to ERAP1, and bulkier residues downstream of the N‐terminus, relative to peptides predominant in the R528 context. None of these differences were observed with ERAP1 variants differing at positions 575/725, but not at residue 528. Neither R528K nor N575D/Q725R altered the mean length of B*27:05‐bound ligands.
Conclusion
The R528K, but not the N575D/Q725R, polymorphism alters the expression levels of many HLA–B*27:05–bound peptides, depending on the susceptibility of their N‐terminal residues to trimming and depending on the size of the amino acid side chains at multiple positions downstream of the N‐terminus. The significant alterations in the B*27:05 peptidome and the structural features of the peptides that determine their differential expression in distinct ERAP1 contexts account for the association of the R528K polymorphism with AS.
A low-activity variant of endoplasmic reticulum aminopeptidase 1 (ERAP1), Hap10, is associated with the autoinflammatory disorder Behçet's disease (BD) in epistasis with HLA-B*51, which is the main ...risk factor for this disorder. The role of Hap10 in BD pathogenesis is unknown. We sought to define the effects of Hap10 on the HLA-B*51 peptidome and to distinguish these effects from those due to HLA-B*51 polymorphisms unrelated to disease. The peptidome of the BD-associated HLA-B*51:08 subtype expressed in a Hap10-positive cell line was isolated, characterized by mass spectrometry, and compared with the HLA-B*51:01 peptidome from cells expressing more active ERAP1 allotypes. We additionally performed synthetic peptide digestions with recombinant ERAP1 variants and estimated peptide-binding affinity with standard algorithms. In the BD-associated ERAP1 context of B*51:08, longer peptides were generated; of the two major HLA-B*51 subpeptidomes with Pro-2 and Ala-2, the former one was significantly reduced, and the latter was increased and showed more ERAP1-susceptible N-terminal residues. These effects were readily explained by the low activity of Hap10 and the differential susceptibility of X–Pro and X–Ala bonds to ERAP1 trimming and together resulted in a significantly altered peptidome with lower affinity. The differences due to ERAP1 were clearly distinguished from those due to HLA-B*51 subtype polymorphism, which affected residue frequencies at internal positions of the peptide ligands. The alterations in the nature and affinity of HLA-B*51·peptide complexes probably affect T-cell and natural killer cell recognition, providing a sound basis for the joint association of ERAP1 and HLA-B*51 with BD.
Background
Gliomas in dogs remain poorly understood.
Objectives
To characterize the clinicopathologic findings, diagnostic imaging features and survival of a large sample of dogs with glioma using ...the Comparative Brain Tumor Consortium diagnostic classification.
Animals
Ninety‐one dogs with histopathological diagnosis of glioma.
Methods
Multicentric retrospective case series. Signalment, clinicopathologic findings, diagnostic imaging characteristics, treatment, and outcome were used. Tumors were reclassified according to the new canine glioma diagnostic scheme.
Results
No associations were found between clinicopathologic findings or survival and tumor type or grade. However, definitive treatments provided significantly (P = .03) improved median survival time (84 days; 95% confidence interval CI, 45‐190) compared to palliative treatment (26 days; 95% CI, 11‐54). On magnetic resonance imaging (MRI), oligodendrogliomas were associated with smooth margins and T1‐weighted hypointensity compared to astrocytomas (odds ratio OR, 42.5; 95% CI, 2.42‐744.97; P = .04; OR, 45.5; 95% CI, 5.78‐333.33; P < .001, respectively) and undefined gliomas (OR, 84; 95% CI, 3.43‐999.99; P = .02; OR, 32.3; 95% CI, 2.51‐500.00; P = .008, respectively) and were more commonly in contact with the ventricles than astrocytomas (OR, 7.47; 95% CI, 1.03‐53.95; P = .049). Tumor spread to neighboring brain structures was associated with high‐grade glioma (OR, 6.02; 95% CI, 1.06‐34.48; P = .04).
Conclusions and Clinical Importance
Dogs with gliomas have poor outcomes, but risk factors identified in survival analysis inform prognosis and the newly identified MRI characteristics could refine diagnosis of tumor type and grade.
Objective
To determine the influence of endoplasmic reticulum aminopeptidase 2 (ERAP‐2) expression on the HLA–B*27 peptidome in live cells.
Methods
Using immunoaffinity chromatography and acid ...extraction, HLA–B*27:05–bound peptides were isolated from 2 ERAP‐2–negative lymphoblastoid cell lines and 1 ERAP‐2–positive lymphoblastoid cell line expressing functionally indistinguishable ERAP‐1 variants. More than 2,000–4,000 B*27:05 ligands were identified from each cell line, and their relative abundance was established by quantitative tandem mass spectrometry and MaxQuant‐based peptide analyses. Pairwise comparisons were used to determine the structural features of peptides whose relative abundance was dependent on the presence of ERAP‐2. Synthetic peptide digestions were performed with recombinant ERAP‐1 and ERAP‐2. Peptide affinity was estimated with standard algorithms.
Results
The B*27:05 peptidome from ERAP‐2–positive cells showed 3–4% fewer peptides with N‐terminal basic residues than did the peptidome from ERAP‐2–negative cells. Among the shared peptides, those most abundant in the presence of ERAP‐2 included more nonamers, fewer decamers, and fewer N‐terminal basic residues than the peptides predominant in ERAP‐2–negative cells. These ERAP‐2–dependent changes did not alter the global affinity of the B*27:05 peptidome.
Conclusion
ERAP‐2 significantly influences the B*27:05‐bound peptidome by destroying some ligands and decreasing the abundance of many more ligands with N‐terminal basic residues, while increasing the abundance of nonamers. The former effects are best explained by direct ERAP‐2 trimming. The effects on peptide length might be attributed to ERAP‐2–induced activation of ERAP‐1 trimming. These data support the notion of a peptide‐mediated mechanism as the basis for the association of ERAP‐2 with ankylosing spondylitis. Analogous effects on other major histocompatibility complex class I peptidomes might explain the involvement of ERAP‐2 in HLA–B27–negative spondyloarthritis.
A stereolithography-based additive manufacturing technique has been used for the fabrication of advanced ceramics. A customised 3D printer using a Digital Light Processing (DLP) projector as UV ...source has been built to fabricate green bodies from photosensitive resins loaded with 25–60wt% of alumina, 3- and 8-YSZ. The 3D-printed bodies were then sintered in the 1200–1500°C and exhibited thermal stability. As expected, higher ceramic loadings rendered objects with higher density for a given sintering temperature. The limit of solid loading in the resin is approximately 60% and beyond those contents, the extra ceramic appears as powder loosely adhered to the sintered objects. Photogrammetry was used to evaluate the accuracy of the 3D printing process and highlighted a marked deviation between the CAD model and the resulting object, particularly in the top part of the specimens, possibly due to the use of volatile solvents which cause changes in the photoresins used. Nevertheless, that problem may be overcome by thermostatising the printer vat and/or using solvents with higher boiling point. The results obtained suggest the potential application of low cost DLP 3D printing techniques to process ceramics for a number of applications including ceramic fuel cells, piezoelectrics, dental applications, etc.
Se ha empleado una técnica de fabricación aditiva basada en la estereolitografía para la producción de cerámicas avanzadas. Se ha diseñado y construido una impresora 3D personalizada empleando como fuente de UV un proyector DLP para fabricar cuerpos verdes a partir de resinas fotosensibles cargadas con el 25-60% en peso de alúmina, 3-YSZ y 8-YSZ. Los cuerpos impresos mostraron estabilidad térmica tras los correspondientes tratamientos de sinterización entre 1.200 y 1.500°C. Como era de esperar, los mayores contenidos de sólido en las resinas dieron lugar a objetos con mayores densidades relativas para cada temperatura de sinterización. El límite de carga sólida en las resinas es aproximadamente un 60%, y por encima de estas cantidades, el contenido extra de cerámico aparece como partículas de polvo débilmente adheridas a los objetos sinterizados. Se empleó la fotogrametría para evaluar la precisión del proceso de impresión 3D donde se puso de manifiesto una marcada diferencia entre el modelo CAD y el objeto impreso, especialmente en la parte superior de los especímenes, posiblemente debido al uso de disolventes volátiles que provocan cambios en las fotorresinas empleadas. Sin embargo, este problema puede paliarse termostatizando el contenedor de la resina de la impresora y/o mediante el empleo de disolventes con mayor punto de ebullición. Los resultados obtenidos sugieren la potencial aplicación de técnicas de impresión 3D DLP de bajo coste para el procesado de cerámicos para aplicaciones como pilas de combustible cerámicas, piezoeléctricos, aplicaciones dentales, etc.
Objective
To characterize the peptidome of the Behçet's disease–associated HLA–B*51:01 allotype as well as the differential features of major peptide subsets and their distinct endoplasmic reticulum ...aminopeptidase 1 (ERAP‐1)–mediated processing.
Methods
The endogenous B*51:01‐bound peptidome was characterized from 721.221 transfectant cells, after affinity chromatography and acid extraction, by tandem mass spectrometry. Recombinant ERAP‐1 variants were used to digest synthetic B*51:01 ligands. HLA and transporter associated with antigen processing (TAP) binding affinities of peptide ligands were calculated with well‐established algorithms. ERAP‐1 and ERAP‐2 from 721.221 cells were characterized by genomic sequencing and Western blotting.
Results
The B*51:01 peptidome consisted of 29.5% octamers, 61.7% nonamers, 4.8% decamers, and 4.0% longer peptides. The major peptide motif consisted of Pro and Ala at position 2, aliphatic/aromatic position 3 residues, and Val and Ile at the C‐terminal position. The ligands with Pro or Ala at position 2 constituted 2 distinct subpeptidomes. Peptides with Pro at position 2 showed higher affinity for B*51:01 and lower affinity for TAP than those with Ala at position 2. Most important, both peptide subsets differed drastically in the susceptibility of their position 1 residues to ERAP‐1, revealing a distinct influence of this enzyme on both subpeptidomes, which may alter their balance, affecting the global affinity of B*51:01–peptide complexes.
Conclusion
ERAP‐1 has a significant influence on the B*51:01 peptidome and its affinity. This influence is based on very distinct effects on the 2 subpeptidomes, whereby only peptides in the subpeptidome with Ala at position 2 are extensively destroyed, except when their position 1 residues are ERAP‐1 resistant. This pattern provides a mechanism for the epistatic association of ERAP‐1 and B*51:01 in Behçet's disease.
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