Knowledge Domains, Technological Strategies and Open Innovation

This study provides a patent-based framework, investigating the relationship among the relevance of the technological domains, the exploitation vs. exploration strategies and the choice of open innovation practices. Specifically, this work presents five levels of open innovation adoption and analyses the reason why firms open up their innovation boundaries. The methodology is tested on a sample of 240 companies belonging to the bio-pharmaceutical and the technology hardware & equipment industries, by examining their patents filed in 2011. Results show that the relevance of the knowledge domain affects the choice of the innovation strategy; also, non-equity alliances are preferred in explorative activities and equity alliances in exploitative ones

A Novel Aspartyl Proteinase from Apocrine Epithelia and Breast Tumors

Abstract GCDFP-15 (gross cysticdisease fluid protein,15 kDa) is a secretory marker of apocrine differentiation in breast carcinoma. In human breast cancer cell lines, gene expression is regulated by hormones, including androgens and prolactin. The protein is also known under different names in different body fluids such as gp17 in seminal plasma. GCDFP-15/gp17 is a ligand of CD4 and is a potent inhibitor of T-cell apoptosis induced by sequential CD4/T-cell receptor triggering. We now report that GCDFP-15/gp17 is a protease exhibiting structural properties relating it to the aspartyl proteinase superfamily. Unexpectedly, GCDFP-15/gp17 appears to be related to the retroviral members rather than to the known cellular members of this class. Site-specific mutagenesis of Asp22 (predicted to be catalytically important for the active site) and pepstatin A inhibition confirmed that the protein is an aspartic-type protease. We also show that, among the substrates tested, GCDFP-15/gp17 is specific for fibronectin. The study of GCDFP-15/gp17-mediated proteolysis may provide a handle to understand phenomena as diverse as mammary tumor progression and fertilization

The Aes protein and the monomeric alpha-galactosidase from Escherichia coli form a non-covalent complex. Implications for the regulation of carbohydrate metabolism.

Aes, a 36-kDa acetylesterase fromEscherichia coli, belongs to the hormone-sensitive lipase family, and it is involved in the regulation of MalT, the transcriptional activator of the maltose regulon. The activity of MalT is depressed through a direct protein-protein interaction with Aes. Although the effect is clear-cut, the meaning of this interaction and the conditions that trigger it still remain elusive. To perform a comparative thermodynamic study between the mesophilic Aes protein and two homologous thermostable enzymes, Aes was overexpressed in E. coli and purified. At the last step of the purification procedure the enzyme was eluted from a Mono Q HR 5/5 column as a major form migrating, anomalously, at 56 kDa on a calibrated Superdex 75 column. A minor peak that contains the Aes protein and a polypeptide of 50 kDa was also detected. By a combined analysis of size-exclusion chromatography and surface-enhanced laser desorption ionization-time of flight mass spectrometry, it was possible to demonstrate the presence in this peak of a stable 87-kDa complex, containing the Aes protein itself and the 50-kDa polypeptide in a 1:1 ratio. The homodimeric molecular species of Aes and of the 50-kDa polypeptide were also detected. The esterase activity associated with the 87-kDa complex, when assayed with p-nitrophenyl butanoate as substrate, proved 6-fold higher than the activity of the major Aes form of 56 kDa. Amino-terminal sequencing highlighted that the 50-kDa partner of Aes in the complex was the α-galactosidase from E. coli. TheE. coli cells harboring plasmid pT7-SCII-aesand, therefore, expressing Aes were hampered in their growth on a minimal medium containing raffinose as a sole carbon source. Because α-galactosidase is involved in the metabolism of raffinose, the above findings suggest a potential role of Aes in the regulation of carbohydrate metabolism in E. coli

Patent data analysis of innovation behaviours in technology hardware & equipment industry

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Investments and Divestments of Intangibles in an Open Innovation Context

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Business Models for Open Innovation: From Collaboration to Incorporation

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AurkA inhibitors enhance the effects of B-RAF and MEK inhibitors in melanoma treatment

Background: Aurora kinase A (AurkA) is over-expressed in melanoma and its inhibition has been observed to limit tumor growth, suggesting a potential role in melanoma treatment. Methods: A human melanoma cell line with the B-RAF (V600E) mutation (A375mel) was exposed to B-RAF inhibitor (GSK2118436), MEK inhibitor (GSK1120212) and AurkA inhibitor (MLN8054) as single agents or in various combinations (BRAF plus AurkA inhibitor, MEK plus AurkA inhibitor or triple combination BRAF plus MEK plus AurkA inhibitor). Cell proliferation was assessed using xCELLigence technology. Total protein extracts were examined for p53 and c-Myc protein expression by Western blot analysis. Drug anti-tumor effects were further assessed using a 3D-human melanoma skin reconstruction model, in which tissues were incubated with serum-free medium containing control, B-RAF plus MEK inhibitor, MEK plus AurkA inhibitor or the triple combination. Results: AurkA inhibitor plus B-RAF inhibitor, AurkA inhibitor plus MEK inhibitor or triple combination had a markedly greater anti-proliferative effect on A375 (BRAFV600E) melanoma cells than single agents. In the 3D human skin model, the triple combination had a greater anti-tumor effect at the epidermal/dermal junction than control or either double combination. However, S-100 and Ki-67 positively stained spindle-shaped cells were detected in the dermal stratum, suggesting the presence of alive and proliferating melanoma cells. Conclusions: These findings provide new prospects for melanoma research, including combined B-RAF/AurkA inhibition for B-RAF mutated melanomas and MEK/AurkA inhibitor combination for patients without B-RAF mutations. Moreover, for the first time, we have shown that a B-RAF, MEK and AurkA inhibitor triple drug combination offers increased efficacy against melanoma cell growth and might be considered as a potential treatment strategy for enhancing clinical response in melanoma. However, although this triple drug combination was more effective at the epidermal/dermal junction, the suggested presence of alive and proliferating melanoma cells in the dermal stratum could result in drug resistance and disease recurrence. Molecular characterization of these dermal cells may be critical for the development of novel therapeutic strategies

Mutations impairing GSK3-mediated MAF phosphorylation cause cataract, deafness, intellectual disability, seizures, and a down syndrome-like facies

Transcription factors operate in developmental processes to mediate inductive events and cell competence, and perturbation of their function or regulation can dramatically affect morphogenesis, organogenesis, and growth. We report that a narrow spectrum of amino-acid substitutions within the transactivation domain of the v-maf avian musculoaponeurotic fibrosarcoma oncogene homolog (MAF), a leucine zipper-containing transcription factor of the AP1 superfamily, profoundly affect development. Seven different de novo missense mutations involving conserved residues of the four GSK3 phosphorylation motifs were identified in eight unrelated individuals. The distinctive clinical phenotype, for which we propose the eponym Aymé-Gripp syndrome, is not limited to lens and eye defects as previously reported for MAF/Maf loss of function but includes sensorineural deafness, intellectual disability, seizures, brachycephaly, distinctive flat facial appearance, skeletal anomalies, mammary gland hypoplasia, and reduced growth. Disease-causing mutations were demonstrated to impair proper MAF phosphorylation, ubiquitination and proteasomal degradation, perturbed gene expression in primary skin fibroblasts, and induced neurodevelopmental defects in an in vivo model. Our findings nosologically and clinically delineate a previously poorly understood recognizable multisystem disorder, provide evidence for MAF governing a wider range of developmental programs than previously appreciated, and describe a novel instance of protein dosage effect severely perturbing developmen

Dante nelle letterature straniere

Il volume offre un incrocio di sguardi critici sulle rotte percorse dall’opera dantesca nelle letterature straniere. A settecento anni dalla sua morte, la voce di Dante continua a oltrepassare confini permeando immaginari lontani, in un incedere di evocazioni, traduzioni, interpretazioni e riscritture. I venti saggi qui presentati tratteggiano un itinerario di esplorazione delle tracce dantesche nelle tradizioni letterarie di Albania, Svezia, Francia, Cuba, Polonia, Stati Uniti, Germania, Argentina, Danimarca, Scozia, Inghilterra e Messico. Le diverse latitudini abbracciate si articolano in una raccolta di studi che dall’epoca moderna confluisce nell’estremo contemporaneo, calibrando nuovi orizzonti e prospettive nello sconfinato territorio della critica dantesca. Gli autori e le autrici illuminano storie di ricezione, riletture e dialoghi intertestuali nei quali la memoria della Commedia si riconfigura in un’inesauribile pluralità di scritture, di cui si intende consegnare in queste pagine uno sguardo di carattere esplorativo e non antologico. La parola di Dante attraversa lingue e universi letterarioculturali senza tradirsi ma conoscendo nuove fioriture: confermandosi una parola necessaria, profetica e viva

Adherencia al tratamiento de pacientes con artritis reumatoidea que reciben medicamentos biológicos

Introducción: Al igual que en otras enfermedades crónicas, la adherencia al régimen terapéutico de los pacientes con artritis reumatoidea (AR) es baja (entre 30 y 80%), dependiendo de la definición de adherencia y de la metodología empleada para medirla. En este estudio se propone determinar el nivel de adherencia al tratamiento en pacientes con AR que reciben DMAR biológicas e identificar factores asociados a la falta de cumplimiento a la terapia. Material y métodos: Se realizó un estudio analítico, observacional de corte transversal en donde se incluyeron pacientes consecutivos con AR según criterios de clasificación (ACR’87) que se encontraban recibiendo fármacos biológicos para el tratamiento de su enfermedad en los últimos seis meses y que asistieron a la consulta ambulatoria. Para la valoración de la adherencia a DMAR se utilizaron los cuestionarios CQR (Compliance Questionnaire on Rheumatology) y el cuestionario SMAQ (Simplified Medication Adherence Questionnaire). Resultados: Se encuestaron 345 pacientes. Mediante el cuestionario SMAQ se observó una adherencia del 50% (159 pacientes). El Cuestionario CQR tuvo un puntaje mediano de 78 puntos (RIC 67-86). El 47% (147 pacientes) fueron adherentes (CQR >80). Sobre los pacientes incluidos, 151 (48%) refirieron no haber tenido ningún retraso, pérdida o adelanto de la dosis del biológico en los últimos 6 meses de tratamiento. El 52% no adherentes tuvo como causas: 146 (46%) pérdida de al menos una dosis del biológico con una mediana de dosis perdidas de 2 (RIQ: 1-3); 117 (37%) tuvo al menos un retraso en las dosis del biológico y 8 (2%) delantó la dosis. Los factores asociados al no cumplimiento de la terapia biológica fueron el tipo de cobertura médica, que el paciente no haya notado mejoría y la esperanza de una rápida respuesta al tratamiento, y la falta de adherencia a DMAR