Coping with Technology: A Study on Economic Methodology and Strategic Management of Technology

There is a broad consensus among economists that technologicalchange has been a major contributor to the productivity growth and, hence, to the growth of the material welfare in western industrialized countries at least over the last century. Paradoxically, this issue has not been the focal point of theoretical economics. At the same time, we have witnessed the rise of the importance of technological issues at the strategic management level of business firms. Interestingly, the research has not accurately responded to this challenge either. The tension between the overwhelming empirical evidence of the importance of technology and its relative omission in the research offers a challenging target for a methodological endeavor. This study deals with the question of how different theories cope with technology and explain technological change. The focusis at the firm level and the analysis concentrates on metatheoretical issues, except for the last two chapters, which examine the problems of strategic management of technology. Here the aim is to build a new evolutionary-based theoreticalframework to analyze innovation processes at the firm level. The study consistsof ten chapters. Chapter 1 poses the research problem and contrasts the two basic approaches, neoclassical and evolutionary, to be analyzed. Chapter 2 introduces the methodological framework which is based on the methodology of isolation. Methodological and ontoogical commitments of the rival approaches are revealed and basic questions concerning their ways of theorizing are elaborated. Chapters 3-6 deal with the so-called substantive isolative criteria. The aim is to examine how different approaches cope with such critical issues as inherent uncertainty and complexity of innovative activities (cognitive isolations, chapter 3), theboundedness of rationality of innovating agents (behavioral isolations, chapter4), the multidimensional nature of technology (chapter 5), and governance costsrelated to technology (chapter 6). Chapters 7 and 8 put all these things together and look at the explanatory structures used by the neoclassical and evolutionary approaches in the light of substantive isolations. The last two cpahters of the study utilize the methodological framework and tools to appraise different economics-based candidates in the context of strategic management of technology. The aim is to analyze how different approaches answer the fundamental question: How can firms gain competitive advantages through innovations and how can the rents appropriated from successful innovations be sustained? The last chapter introduces a new evolutionary-based technology management framework. Also the largely omitted issues of entrepreneurship are examined.

Tipologías de viveros de empresas: tradicionales y especializados

A través del presente estudio empírico se detecta que existen dos tipos de viveros de empresas. Los viveros tradicionales se centran en la promoción de nuevas empresas que desde un buen inicio tengan unas ciertas garantías de éxito. En estos viveros conviven empresas que representan a una amplia gama de sectores empresariales. Los principales requisitos de entrada (obligatorios) son un plan de viabilidad económica y técnica, además de que la empresa sea de reciente creación. Los viveros especializados son aquellos que priman iniciativas empresariales relacionadas con un sector concreto: frecuentemente las empresas relacionadas con las nuevas tecnologías de la información y comunicación (TIC).

Genome-wide profiling of the cardiac transcriptome after myocardial infarction identifies novel heart-specific long non-coding RNAs.

AIM: Heart disease is recognized as a consequence of dysregulation of cardiac gene regulatory networks. Previously, unappreciated components of such networks are the long non-coding RNAs (lncRNAs). Their roles in the heart remain to be elucidated. Thus, this study aimed to systematically characterize the cardiac long non-coding transcriptome post-myocardial infarction and to elucidate their potential roles in cardiac homoeostasis. METHODS AND RESULTS: We annotated the mouse transcriptome after myocardial infarction via RNA sequencing and ab initio transcript reconstruction, and integrated genome-wide approaches to associate specific lncRNAs with developmental processes and physiological parameters. Expression of specific lncRNAs strongly correlated with defined parameters of cardiac dimensions and function. Using chromatin maps to infer lncRNA function, we identified many with potential roles in cardiogenesis and pathological remodelling. The vast majority was associated with active cardiac-specific enhancers. Importantly, oligonucleotide-mediated knockdown implicated novel lncRNAs in controlling expression of key regulatory proteins involved in cardiogenesis. Finally, we identified hundreds of human orthologues and demonstrate that particular candidates were differentially modulated in human heart disease. CONCLUSION: These findings reveal hundreds of novel heart-specific lncRNAs with unique regulatory and functional characteristics relevant to maladaptive remodelling, cardiac function and possibly cardiac regeneration. This new class of molecules represents potential therapeutic targets for cardiac disease. Furthermore, their exquisite correlation with cardiac physiology renders them attractive candidate biomarkers to be used in the clinic.

Targeting Enterococcus faecalis Biofilms with Phage Therapy.

Phage therapy has been proven to be more effective, in some cases, than conventional antibiotics, especially regarding multidrug-resistant biofilm infections. The objective here was to isolate an anti-Enterococcus faecalis bacteriophage and to evaluate its efficacy against planktonic and biofilm cultures. E. faecalis is an important pathogen found in many infections, including endocarditis and persistent infections associated with root canal treatment failure. The difficulty in E. faecalis treatment has been attributed to the lack of anti-infective strategies to eradicate its biofilm and to the frequent emergence of multidrug-resistant strains. To this end, an anti-E. faecalis and E. faecium phage, termed EFDG1, was isolated from sewage effluents. The phage was visualized by electron microscopy. EFDG1 coding sequences and phylogeny were determined by whole genome sequencing (GenBank accession number KP339049), revealing it belongs to the Spounavirinae subfamily of the Myoviridae phages, which includes promising candidates for therapy against Gram-positive pathogens. This analysis also showed that the EFDG1 genome does not contain apparent harmful genes. EFDG1 antibacterial efficacy was evaluated in vitro against planktonic and biofilm cultures, showing effective lytic activity against various E. faecalis and E. faecium isolates, regardless of their antibiotic resistance profile. In addition, EFDG1 efficiently prevented ex vivo E. faecalis root canal infection. These findings suggest that phage therapy using EFDG1 might be efficacious to prevent E. faecalis infection after root canal treatment.

Identifying the index lesion with template prostate mapping biopsies.

PURPOSE: The natural history of prostate cancer might be driven by the index lesion. We determined the percent of men in whom the index lesion could be defined using transperineal template prostate mapping biopsies. MATERIALS AND METHODS: Included in study were consecutive men undergoing transperineal template prostate mapping biopsies with biopsies grouped into 20 zones. Men with clinically significant disease in only 1 prostate area were considered to have an identifiable index lesion. We evaluated the impact of using 2 definitions of clinically significant disease (Gleason grade pattern 4 and/or lesion volume 0.5 cc or greater) and 2 clustering rules (stringent and tolerant) to define the index lesion. RESULTS: Included in study were 391 men with a median age of 62 years (IQR 58-67) and a median prostate specific antigen of 6.9 ng/ml (IQR 4.8-10.0). Of the men 269 (69%) were previously diagnosed with prostate cancer. By deploying a median of 1.2 cores per ml (IQR 0.9-1.7) cancer was diagnosed in 82.9% of the men (324 of 391) with a median of 6 positive cores (IQR 2-9), a median maximum cancer core length of 5 mm (IQR 3-8) and a total cancer core length per zone of 7 mm (IQR 3-13). Insignificant disease was found in 26.3% to 42.9% of cases. When a stringent spatial relationship was used to define individual lesions, 44.4% to 54.6% of patients had 1 index lesion and 12.7% to 19.1% had more than 1 area with clinically significant disease. These proportions changed to 46.6% to 59.2% and 10.5% to 14.5%, respectively, when less stringent spatial clustering was applied. CONCLUSIONS: Transperineal template prostate mapping biopsies enable the index lesion to be localized in most men with clinically significant disease. This information may be important to select appropriate candidates for targeted therapy and to plan a tailored treatment strategy in men undergoing radical therapy.

Historias de vida en educación: biografías en contexto

[spa] Esta publicación recoge los trabajos presentados en las I Jornadas de Historias de Vida en Educación: Cuestiones epistemológicas, metodológicas, éticas y de formación que, organizadas por el grupo de investigación consolidado ESBRINA (Subjetividades y entornos educativos contemporáneos -2009SGR 503), se celebraron en el Departamento de Didáctica y Organización Educativa de la Universidad de Barcelona los días 10 y 11 de junio de 2010.A las mismas asistieron unas 50 personas -docentes e investigadores universitarios y estudiantes de máster y doctorado de España, Portugal, México, Chile, Italia, Francia y Brasil- quienes, después de una introducción por parte de las personas que coordinaban los temas, debatieron con intensidad las cuestiones que emergieron de la lectura de las contribuciones que algunos de los participantes enviaron previamente. Con posterioridad, la mayoría revisaron sus presentaciones para acomodarla al formato de esta publicación.

Historias de vida en educación: biografías en contexto

[spa] Esta publicación recoge los trabajos presentados en las I Jornadas de Historias de Vida en Educación: Cuestiones epistemológicas, metodológicas, éticas y de formación que, organizadas por el grupo de investigación consolidado ESBRINA (Subjetividades y entornos educativos contemporáneos -2009SGR 503), se celebraron en el Departamento de Didáctica y Organización Educativa de la Universidad de Barcelona los días 10 y 11 de junio de 2010.A las mismas asistieron unas 50 personas -docentes e investigadores universitarios y estudiantes de máster y doctorado de España, Portugal, México, Chile, Italia, Francia y Brasil- quienes, después de una introducción por parte de las personas que coordinaban los temas, debatieron con intensidad las cuestiones que emergieron de la lectura de las contribuciones que algunos de los participantes enviaron previamente. Con posterioridad, la mayoría revisaron sus presentaciones para acomodarla al formato de esta publicación.

Historias de vida en educación: biografías en contexto

[spa] Esta publicación recoge los trabajos presentados en las I Jornadas de Historias de Vida en Educación: Cuestiones epistemológicas, metodológicas, éticas y de formación que, organizadas por el grupo de investigación consolidado ESBRINA (Subjetividades y entornos educativos contemporáneos -2009SGR 503), se celebraron en el Departamento de Didáctica y Organización Educativa de la Universidad de Barcelona los días 10 y 11 de junio de 2010.A las mismas asistieron unas 50 personas -docentes e investigadores universitarios y estudiantes de máster y doctorado de España, Portugal, México, Chile, Italia, Francia y Brasil- quienes, después de una introducción por parte de las personas que coordinaban los temas, debatieron con intensidad las cuestiones que emergieron de la lectura de las contribuciones que algunos de los participantes enviaron previamente. Con posterioridad, la mayoría revisaron sus presentaciones para acomodarla al formato de esta publicación.

Mid-gut ACTH-secreting neuroendocrine tumor unmasked with (18)F-dihydroxyphenylalanine-positron emission tomography.

Ectopic ACTH Cushing's syndrome (EAS) is often caused by neuroendocrine tumors (NETs) of lungs, pancreas, thymus, and other less frequent locations. Localizing the source of ACTH can be challenging. A 64-year-old man presented with rapidly progressing fatigue, muscular weakness, and dyspnea. He was in poor condition and showed facial redness, proximal amyotrophy, and bruises. Laboratory disclosed hypokalemia, metabolic alkalosis, and markedly elevated ACTH and cortisol levels. Pituitary was normal on magnetic resonance imaging (MRI), and bilateral inferior petrosal sinus blood sampling with corticotropin-releasing hormone stimulation showed no significant central-to-periphery gradient of ACTH. Head and neck, thoracic and abdominal computerized tomography (CT), MRI, somatostatin receptor scintigraphy (SSRS), and (18)F-deoxyglucose-positron emission tomography (FDG-PET) failed to identify the primary tumor. (18)F-dihydroxyphenylalanine (F-DOPA)-PET/CT unveiled a 20-mm nodule in the jejunum and a metastatic lymph node. Segmental jejunum resection showed two adjacent NETs, measuring 2.0 and 0.5 cm with a peritoneal metastasis. The largest tumor expressed ACTH in 30% of cells. Following surgery, after a transient adrenal insufficiency, ACTH and cortisol levels returned to normal values and remain normal over a follow-up of 26 months. Small mid-gut NETs are difficult to localize on CT or MRI, and require metabolic imaging. Owing to low mitotic activity, NETs are generally poor candidates for FDG-PET, whereas SSRS shows poor sensitivity in EAS due to intrinsically low tumor concentration of type-2 somatostatin receptors (SST2) or to receptor down regulation by excess cortisol. However, F-DOPA-PET, which is related to amine precursor uptake by NETs, has been reported to have high positive predictive value for occult EAS despite low sensitivity, and constitutes a useful alternative to more conventional methods of tumor localization. LEARNING POINTS: Uncontrolled high cortisol levels in EAS can be lethal if untreated.Surgical excision is the keystone of NETs treatment, thus tumor localization is crucial.Most cases of EAS are caused by NETs, which are located mainly in the lungs. However, small gut NETs are elusive to conventional imaging and require metabolic imaging for detection.FDG-PET, based on tumor high metabolic rate, may not detect NETs that have low mitotic activity. SSRS may also fail, due to absent or low concentration of SST2, which may be down regulated by excess cortisol.F-DOPA-PET, based on amine-precursor uptake, can be a useful method to localize the occult source of ACTH in EAS when other methods have failed.

First evidence for the two-body charmless baryonic decay

The results of a search for the rare two-body charmless baryonic decays TeX and TeX are reported. The analysis uses a data sample, corresponding to an integrated luminosity of 0.9 fb−1, of pp collision data collected by the LHCb experiment at a centre-of-mass energy of 7 TeV. An excess of TeX candidates with respect to background expectations is seen with a statistical significance of 3.3 standard deviations. This is the first evidence for a two-body charmless baryonic B 0 decay. No significant TeX signal is observed, leading to an improvement of three orders of magnitude over previous bounds. If the excess events are interpreted as signal, the 68.3% confidence level intervals on the branching fractions are $ TeX $ where the first uncertainty is statistical and the second is systematic.

Strategisen tuotteen materiaalitoimittajan valintaprosessi

Työn tavoitteena on esittää strategisen tuotteen toimittajan valintaprosessi. Tavoitteena on esittää valintaprosessin eri vaiheet ja niissä huomioitavat asiat sekä eri vaiheisiin sovellettavia menetelmiä ja työkaluja.Valintaprosessi alkaa tarpeen määrittämisellä, joka käsittää sekä tuotteen ominaisuuksien että toimittajasuhteen kuvaamisen. Strategisten tuotteiden kohdalla tavoitteena on useimmiten pitkäaikainen yhteistyömuoto valitun toimittajan kanssa. Tarpeen määrittämisen jälkeen etsitään eri lähteistä, kuten erilaisista kaupallisista hakemistoista, internetistä, ammattijulkaisuista sekä henkilökohtaisten kontaktien avulla, potentiaalisia toimittajia, joista luodaan ehdokaslista. Seuraavana on vuorossa sovellettavien valintakriteerien määrittäminen. Tyypillisesti tarkastellaan ainakin toimittajan taloudellista tilannetta, laatua, tuotantoa, kuljetusta, palvelua ja raportointia ja tiedonvälitystä. Tämän jälkeen suoritetaan ensimmäinen seulonta, jossa karsitaan epäsopivimmat ehdokkaat pois prosessin jatkovaiheista. Tarvittavia tietoja voidaan hankkia kirjallisten kyselyiden sekä puhelin- ja henkilöhaastatteluiden avulla. Yksityiskohtaisessa arvioinnissa suoritetaan perusteellinen toimittajien vertailu aikaisemmin valittujen valintakriteerien mukaan. Toimittajan yksityiskohtaiseen arviointiin on tarjolla erilaisia menetelmiä, kuten luokiteltu arviointi, painotettu pistearviointi ja kustannussuhdearviointi. Neuvotteluihin valitaan tyypillisesti muutama sopivin toimittaja ja neuvotteluiden jälkeen on pystyttävä valitsemaan sopivin toimittaja tai vaihtoehtoisesti pari toimittajaa, joiden kesken sopimus jaetaan.

Patterns of nucleotide diversity at the regions encompassing the Drosophila insulin-like peptide (dilp) genes: demography vs positive selection in Drosophila melanogaster.

In Drosophila, the insulin-signaling pathway controls some life history traits, such as fertility and lifespan, and it is considered to be the main metabolic pathway involved in establishing adult body size. Several observations concerning variation in body size in the Drosophila genus are suggestive of its adaptive character. Genes encoding proteins in this pathway are, therefore, good candidates to have experienced adaptive changes and to reveal the footprint of positive selection. The Drosophila insulin-like peptides (DILPs) are the ligands that trigger the insulin-signaling cascade. In Drosophila melanogaster, there are several peptides that are structurally similar to the single mammalian insulin peptide. The footprint of recent adaptive changes on nucleotide variation can be unveiled through the analysis of polymorphism and divergence. With this aim, we have surveyed nucleotide sequence variation at the dilp1-7 genes in a natural population of D. melanogaster. The comparison of polymorphism in D. melanogaster and divergence from D. simulans at different functional classes of the dilp genes provided no evidence of adaptive protein evolution after the split of the D. melanogaster and D. simulans lineages. However, our survey of polymorphism at the dilp gene regions of D. melanogaster has provided some evidence for the action of positive selection at or near these genes. The regions encompassing the dilp1-4 genes and the dilp6 gene stand out as likely affected by recent adaptive events.

Predicting drug metabolism: experiment and/or computation?

Drug metabolism can produce metabolites with physicochemical and pharmacological properties that differ substantially from those of the parent drug, and consequently has important implications for both drug safety and efficacy. To reduce the risk of costly clinical-stage attrition due to the metabolic characteristics of drug candidates, there is a need for efficient and reliable ways to predict drug metabolism in vitro, in silico and in vivo. In this Perspective, we provide an overview of the state of the art of experimental and computational approaches for investigating drug metabolism. We highlight the scope and limitations of these methods, and indicate strategies to harvest the synergies that result from combining measurement and prediction of drug metabolism.

Dysfunctional SEMA3E signaling underlies gonadotropin-releasing hormone neuron deficiency in Kallmann syndrome.

Individuals with an inherited deficiency in gonadotropin-releasing hormone (GnRH) have impaired sexual reproduction. Previous genetic linkage studies and sequencing of plausible gene candidates have identified mutations associated with inherited GnRH deficiency, but the small number of affected families and limited success in validating candidates have impeded genetic diagnoses for most patients. Using a combination of exome sequencing and computational modeling, we have identified a shared point mutation in semaphorin 3E (SEMA3E) in 2 brothers with Kallmann syndrome (KS), which causes inherited GnRH deficiency. Recombinant wild-type SEMA3E protected maturing GnRH neurons from cell death by triggering a plexin D1-dependent (PLXND1-dependent) activation of PI3K-mediated survival signaling. In contrast, recombinant SEMA3E carrying the KS-associated mutation did not protect GnRH neurons from death. In murine models, lack of either SEMA3E or PLXND1 increased apoptosis of GnRH neurons in the developing brain, reducing innervation of the adult median eminence by GnRH-positive neurites. GnRH neuron deficiency in male mice was accompanied by impaired testes growth, a characteristic feature of KS. Together, these results identify SEMA3E as an essential gene for GnRH neuron development, uncover a neurotrophic function for SEMA3E in the developing brain, and elucidate SEMA3E/PLXND1/PI3K signaling as a mechanism that prevents GnRH neuron deficiency.

Toimittajavalinta strategiselle komponentille akselistotehtaassa

Diplomityön tavoitteena oli löytää uusi kaarevahampaisten kartiopyörien toimittaja tulevaisuuden tuoteperheelle Sisu Akselit Oy:ssä. Kirjallisuustutkimuksen osuudessa perehdyttiin toimittajanvalintaprosessin eri osa-alueisiin. Käsiteltäviä alueita olivat mm. markkinatekijät, toimittajasuhteen ominaisuudet ja valintaprosessin työvaiheet sekä muutamat prosessin työkalut. Soveltavan osan alussa muodostettiin malli valintaprosessin läpiviemiseksi. Malli koostuu viidestä vaiheesta, joista ensimmäiset neljä toteutettiin diplomityön puitteista. Ensimmäinen vaihe sisältää yrityksen sisäisen analyysin, toinen toimittajamarkkinoiden tutkimuksen yrityksen ulkopuolella, kolmas hankinnan strategiavaihtoehtojen määrittämisen ja neljäs valintojen tekemisen. Viidennessä vaiheessa sovitaan toimituksen yksityiskohdista ja aloitetaan toimitukset. Työn tuloksena saatiin määritettyä toimittajasuhdestrategia Sisu Akselit Oy:n kaarevahampaisten kartiopyörien hankinnalle uudella tuoteperheellä. Valittuun suhdestrategiaan rajattiin suuresta joukosta kolme parhaiten sopivaa potentiaalista toimittajaa. Markkinoilla olevien valmistajien toiminnan tehokkuudessa havaittiin suuria eroja. Näin valintojen tuloksena arvioidaan saavutettavan kustannussäästöjä nykytilaan verrattuna. Työn sivutuotteena syntyi strategisen komponentin toimittajavalintamalli, jota voitaneen yrityksessä soveltaa jatkossakin.