Technological learning and the accumulation of innovation capabilities: evidence from contract manufacturers in Brazil

A pesar de la profusión de estudios sobre aprendizaje como fuente de construcción de competencias tecnológicas en empresas, en general se ha observado dicha relación desde el punto de vista intraempresarial. En este artículo se examina el papel de los flujos interempresariales de conocimiento en la construcción de capacidades de producción y de innovación en filiales de empresas multinacionales del sector de tecnologías de la información y la comunicación (TIC) en Brasil, en el período 1996-2007. Con base en evidencias de primera mano, recogidas por medio de trabajo de campo, se comprobó en el estudio que las empresas investigadas se involucraron los últimos diez años en un proceso de acumulación de capacidades tecnológicas. Sin embargo, se encontró un alto grado de variabilidad entre las empresas en términos de la profundización de acumulación de capacidades tecnológicas, para actividades de producción y de innovación. Gran parte de esa variabilidad es explicada por la naturaleza e intensidad de los procesos interempresariales de aprendizaje desarrollados por las empresas. Este artículo, por tanto, contribuye al entendimiento del proceso de acumulación de capacidades tecnológicas en filiales de empresas multinacionales, en economías emergentes. El artículo también contradice generalizaciones comunes que atribuyen a ese tipo de empresa un papel pasivo, en términos de actividades tecnológicas, en el contexto de economías emergentes.A despeito da profusão de estudos sobre aprendizagem como fonte de construção de competências tecnológicas em empresas, a maioria tem examinado esse relacionamento pela perspectiva intraempresarial. Neste artigo, examina-se o papel dos fluxos interempresariais de conhecimento na construção de capacidades de produção e de inovação em empresas subsidiárias de multinacionais do setor de tecnologias de informação e de comunicação (TICs) do Brasil, no período de 1996 a 2007. Baseando-se em evidências de primeira mão, colhidas por meio de trabalho de campo, constatou-se que as empresas pesquisadas se engajaram ativamente nos últimos dez anos em um processo de acumulação de capacidades tecnológicas. Porém, encontrou-se no estudo alto grau de variabilidade entre as empresas estudadas, em termos da profundidade de acumulação de capacidades tecnológicas para atividades de produção e de inovação. Grande parte dessa variabilidade é explicada pela natureza e pela intensidade dos processos interempresariais de aprendizagem desenvolvidos pelas empresas. Este artigo contribui, portanto, para avançar no entendimento do processo de acumulação tecnológica em subsidiárias de empresas multinacionais em um contexto de economia emergente. Também contradiz generalizações comuns que atribuem a esse tipo de empresa um papel passivo quanto às atividades tecnológicas no contexto de economias emergentes.Despite the profusion of studies on learning as a means of building technological competence in firms, most have examined this relationship from an intra-firm perspective. This article examines the role of cross-firm knowledge flows to build production capacity and innovation in the subsidiaries of multinationals in the sector of information technology and communication (ITC) in Brazil, from 1996 to 2007. Based on first-hand evidence obtained in fieldwork, the study found that, for the last ten years, the companies surveyed have actively engaged in accumulating technological capabilities. However, the study also identified a high degree of variability across companies in terms of the depth of their technological capability accumulation. A substantial part of this variability can be explained by the role of crossorganizational learning processes. This article, therefore, helps to further our understanding of the process of technological accumulation in subsidiaries of multinationals in emerging economies. The study also contradicts common generalizations, according to which this kind of company plays a passive role in emerging economies when it comes to technological activities

Technological learning and the accumulation of innovation capabilities: evidence from contract manufacturers in Brazil

A pesar de la profusión de estudios sobre aprendizaje como fuente de construcción de competencias tecnológicas en empresas, en general se ha observado dicha relación desde el punto de vista intraempresarial. En este artículo se examina el papel de los flujos interempresariales de conocimiento en la construcción de capacidades de producción y de innovación en filiales de empresas multinacionales del sector de tecnologías de la información y la comunicación (TIC) en Brasil, en el período 1996-2007. Con base en evidencias de primera mano, recogidas por medio de trabajo de campo, se comprobó en el estudio que las empresas investigadas se involucraron los últimos diez años en un proceso de acumulación de capacidades tecnológicas. Sin embargo, se encontró un alto grado de variabilidad entre las empresas en términos de la profundización de acumulación de capacidades tecnológicas, para actividades de producción y de innovación. Gran parte de esa variabilidad es explicada por la naturaleza e intensidad de los procesos interempresariales de aprendizaje desarrollados por las empresas. Este artículo, por tanto, contribuye al entendimiento del proceso de acumulación de capacidades tecnológicas en filiales de empresas multinacionales, en economías emergentes. El artículo también contradice generalizaciones comunes que atribuyen a ese tipo de empresa un papel pasivo, en términos de actividades tecnológicas, en el contexto de economías emergentes.A despeito da profusão de estudos sobre aprendizagem como fonte de construção de competências tecnológicas em empresas, a maioria tem examinado esse relacionamento pela perspectiva intraempresarial. Neste artigo, examina-se o papel dos fluxos interempresariais de conhecimento na construção de capacidades de produção e de inovação em empresas subsidiárias de multinacionais do setor de tecnologias de informação e de comunicação (TICs) do Brasil, no período de 1996 a 2007. Baseando-se em evidências de primeira mão, colhidas por meio de trabalho de campo, constatou-se que as empresas pesquisadas se engajaram ativamente nos últimos dez anos em um processo de acumulação de capacidades tecnológicas. Porém, encontrou-se no estudo alto grau de variabilidade entre as empresas estudadas, em termos da profundidade de acumulação de capacidades tecnológicas para atividades de produção e de inovação. Grande parte dessa variabilidade é explicada pela natureza e pela intensidade dos processos interempresariais de aprendizagem desenvolvidos pelas empresas. Este artigo contribui, portanto, para avançar no entendimento do processo de acumulação tecnológica em subsidiárias de empresas multinacionais em um contexto de economia emergente. Também contradiz generalizações comuns que atribuem a esse tipo de empresa um papel passivo quanto às atividades tecnológicas no contexto de economias emergentes.Despite the profusion of studies on learning as a means of building technological competence in firms, most have examined this relationship from an intra-firm perspective. This article examines the role of cross-firm knowledge flows to build production capacity and innovation in the subsidiaries of multinationals in the sector of information technology and communication (ITC) in Brazil, from 1996 to 2007. Based on first-hand evidence obtained in fieldwork, the study found that, for the last ten years, the companies surveyed have actively engaged in accumulating technological capabilities. However, the study also identified a high degree of variability across companies in terms of the depth of their technological capability accumulation. A substantial part of this variability can be explained by the role of crossorganizational learning processes. This article, therefore, helps to further our understanding of the process of technological accumulation in subsidiaries of multinationals in emerging economies. The study also contradicts common generalizations, according to which this kind of company plays a passive role in emerging economies when it comes to technological activities

The Role of Calcineurin/NFAT in SFRP2 Induced Angiogenesis—A Rationale for Breast Cancer Treatment with the Calcineurin Inhibitor Tacrolimus

Tacrolimus (FK506) is an immunosuppressive drug that binds to the immunophilin FKBPB12. The FK506-FKBP12 complex associates with calcineurin and inhibits its phosphatase activity, resulting in inhibition of nuclear translocation of nuclear factor of activated T-cells (NFAT). There is increasing data supporting a critical role of NFAT in mediating angiogenic responses stimulated by both vascular endothelial growth factor (VEGF) and a novel angiogenesis factor, secreted frizzled-related protein 2 (SFRP2). Since both VEGF and SFRP2 are expressed in breast carcinomas, we hypothesized that tacrolimus would inhibit breast carcinoma growth. Using IHC (IHC) with antibodies to FKBP12 on breast carcinomas we found that FKBP12 localizes to breast tumor vasculature. Treatment of MMTV-neu transgenic mice with tacrolimus (3 mg/kg i.p. daily) (n = 19) resulted in a 73% reduction in the growth rate for tacrolimus treated mice compared to control (n = 15), p = 0.003; which was associated with an 82% reduction in tumor microvascular density (p<0.001) by IHC. Tacrolimus (1 µM) inhibited SFRP2 induced endothelial tube formation by 71% (p = 0.005) and inhibited VEGF induced endothelial tube formation by 67% (p = 0.004). To show that NFATc3 is required for SFRP2 stimulated angiogenesis, NFATc3 was silenced with shRNA in endothelial cells. Sham transfected cells responded to SFRP2 stimulation in a tube formation assay with an increase in the number of branch points (p<0.003), however, cells transfected with shRNA to NFATc3 showed no increase in tube formation in response to SFRP2. This demonstrates that NFATc3 is required for SFRP2 induced tube formation, and tacrolimus inhibits angiogenesis in vitro and breast carcinoma growth in vivo. This provides a rationale for examining the therapeutic potential of tacrolimus at inhibiting breast carcinoma growth in humans

The relativistic Sagnac Effect: two derivations

The phase shift due to the Sagnac Effect, for relativistic matter and electromagnetic beams, counter-propagating in a rotating interferometer, is deduced using two different approaches. From one hand, we show that the relativistic law of velocity addition leads to the well known Sagnac time difference, which is the same independently of the physical nature of the interfering beams, evidencing in this way the universality of the effect. Another derivation is based on a formal analogy with the phase shift induced by the magnetic potential for charged particles travelling in a region where a constant vector potential is present: this is the so called Aharonov-Bohm effect. Both derivations are carried out in a fully relativistic context, using a suitable 1+3 splitting that allows us to recognize and define the space where electromagnetic and matter waves propagate: this is an extended 3-space, which we call "relative space". It is recognized as the only space having an actual physical meaning from an operational point of view, and it is identified as the 'physical space of the rotating platform': the geometry of this space turns out to be non Euclidean, according to Einstein's early intuition.Comment: 49 pages, LaTeX, 3 EPS figures. Revised (final) version, minor corrections; to appear in "Relativity in Rotating Frames", ed. G. Rizzi and M.L. Ruggiero, Kluwer Academic Publishers, Dordrecht, (2003). See also http://digilander.libero.it/solciclo

An early peak of relapse after surgery for breast cancer

There is great interest among oncologists concerning what we might learn by examining the pattern of relapse after breast cancer surgery. What you see depends upon how hard you look. Up to now, investigators have examined the hazard ratio for relapse every 6–12 months. In a research paper, published in this issue of Breast Cancer Research, the Milan group have looked at the hazard ratio every three months and have found, for the first time, a distinct, very early peak of relapse in a group of premenopausal, node-positive patients not given chemotherapy or hormone therapy. What is now needed is for other groups to repeat this observation and, if found, to examine the characteristics of the tumours producing this phenomenon in order to develop hypotheses about its cause and possible treatments

Simultaneity and generalized connections in general relativity

Stationary extended frames in general relativity are considered. The requirement of stationarity allows to treat the spacetime as a principal fiber bundle over the one-dimensional group of time translations. Over this bundle a connection form establishes the simultaneity between neighboring events accordingly with the Einstein synchronization convention. The mathematics involved is that of gauge theories where a gauge choice is interpreted as a global simultaneity convention. Then simultaneity in non-stationary frames is investigated: it turns to be described by a gauge theory in a fiber bundle without structure group, the curvature being given by the Fr\"olicher-Nijenhuis bracket of the connection. The Bianchi identity of this gauge theory is a differential relation between the vorticity field and the acceleration field. In order for the simultaneity connection to be principal, a necessary and sufficient condition on the 4-velocity of the observers is given.Comment: RevTeX, 9 pages, 2 figures, 1 table. Previous title "The gauge nature of simultaneity". Classical and Quantum Gravity http://www.iop.org/EJ/journal/CQ

Environmental Impact on Vascular Development Predicted by High-Throughput Screening

Background: Understanding health risks to embryonic development from exposure to environmental chemicals is a significant challenge given the diverse chemical landscape and paucity of data for most of these compounds. High-throughput screening (HTS) in the U.S. Environmental Protection Agency (EPA) ToxCast™ project provides vast data on an expanding chemical library currently consisting of > 1,000 unique compounds across > 500 in vitro assays in phase I (complete) and Phase II (under way). This public data set can be used to evaluate concentration-dependent effects on many diverse biological targets and build predictive models of prototypical toxicity pathways that can aid decision making for assessments of human developmental health and disease

A Novel Monoclonal Antibody to Secreted Frizzled-Related Protein 2 Inhibits Tumor Growth

Secreted frizzled related protein 2 (SFRP2) is overexpressed in human angiosarcoma and breast cancer, and stimulates angiogenesis via activation of the calcineurin/ NFATc3 pathway. There are conflicting reports in the literature as to whether SFRP2 is an antagonist or agonist of ß-catenin. The aims of these studies were to assess the effects of SFRP2 antagonism on tumor growth and Wnt-signaling, and to evaluate whether SFRP2 is a viable therapeutic target. The anti-angiogenic and anti-tumor properties of SFRP2 monoclonal antibody (mAb) were assessed using in vitro proliferation, migration, and tube formation assays; and in vivo angiosarcoma and triple negative breast cancer models. Wnt-signaling was assessed in endothelial and tumor cells treated with SFRP2 mAb using Western blotting. Pharmacokinetic (PK) and biodistribution data were generated in tumor-bearing and non-tumor bearing mice. SFRP2 mAb was shown to induce anti-tumor and anti-angiogenic effects in vitro, and inhibit activation of ß-catenin and NFATc3 in endothelial and tumor cells. Treatment of SVR angiosarcoma allografts in nude mice with the SFRP2 mAb decreased tumor volume by 58% compared to control (p=0.004). Treatment of MDA-MB-231 breast carcinoma xenografts with SFRP2 mAb decreased tumor volume by 52% (p=0.03) compared to control, while bevacizumab did not significantly reduce tumor volume. Pharmacokinetic studies show the antibody is long circulating in the blood and preferentially accumulates in SFRP2-positive tumors. In conclusion, antagonizing SFRP2 inhibits activation of ß-catenin and NFATc3 in endothelial and tumor cells, and is a novel therapeutic approach to inhibiting angiosarcoma and triple negative breast cancer

Internal mammary lymph node recurrence: rare but characteristic metastasis site in breast cancer

<p>Abstract</p> <p>Background</p> <p>To assess the frequency of IMLN recurrence, its associated risk factors with disease-free interval (DFI) and its predicting factors on overall survival time.</p> <p>Methods</p> <p>133 cases of breast cancer IMLN recurrence were identified via the computerized CT reporting system between February 2003 and June 2008, during which chest CT for patients with breast cancer (n = 8867) were performed consecutively at Cancer Hospital, Fudan University, Shanghai, China. Patients' charts were retrieved and patients' characteristics, disease characteristics, and treatments after recurrence were collected for analysis. The frequency was 1.5% (133/8867).</p> <p>Results</p> <p>IMLN recurrence was presented as the first metastatic site in 121 (91%) patients while 88 (66.2%) had other concurrent metastases. Typical chest CT images included swelling of the IMLN at the ipsilateral side with local lump and sternal erosion located mostly between the second and third intercostal space. The median disease-free interval (DFI) of IMLN recurrence was 38 months. The independent factors that could delay the IMLN recurrence were small tumor size (HR 0.5 95%CI: 0.4 - 0.8; <it>p </it>= 0.002), and positive ER/PR disease (HR 0.6, 95% CI: 0.4 - 0.9; <it>p </it>= 0.006). The median survival time after IMLN recurrence was 42 months, with a 5-year survival rate of 30%. Univariate analysis showed four variables significantly influenced the survival time: DFI of IMLN recurrence (p = 0.001), no concurrent distant metastasis (p = 0.024), endocrine therapy for patients with positive ER/PR (p = 0.000), radiotherapy (p = 0.040). The independent factors that reduced the death risk were no concurrent distant metastases (HR: 0.7, 95% CI: 0.4 - 0.9; <it>p </it>= 0.031), endocrine therapy for patients with positive ER/PR status (HR: 0.2, 95% CI: 0.1 - 0.5; <it>p </it>= 0.001) and palliative radiotherapy (HR: 0.3, 95% CI: 0.1- 0.9; <it>p </it>= 0.026).</p> <p>Conclusions</p> <p>The risk of IMLN recurrence is low and there are certain characteristics features on CT images. ER/PR status is both a risk factor for DFI of IMLN recurrence and a prognostic factor for overall survival after IMLN recurrence. Patients with only IMLN recurrence and/or local lesion have a good prognosis.</p