73 research outputs found

    Business model analysis of a case company in knowledge intensive business sector Case: Oy Integro Finland Ab

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    This study initiated with the need of analyzing the case company’s business model, and evaluate its suitability to the new market territory of the case company. The objectives of this study include understanding of business model concept and its importance, learning to apply the business model framework to the case company, finally testing and modifying the business model framework of Rajala et.al in a general level of application. The study begins with concept introduction and discussion, include definition of business model, importance of business model, definition of business strategy, introduction of Knowledge-intensive business services, and concept of behavioural analysis/profile etc. Not only include the concepts mentioned before, this study also introduces the development trend of these concept and their relevance to the case company’s situation. The business model framework used in this study was developed by Rajala et al. for software business companies, which share quite much similarities with KIBS companies. After literature review, there is the empirical study of this thesis, which is mainly based on the case company. The empirical study is made based on questionnaires and interviews. The result is analyzed based on Rajala et al.’ business model framework (2001). Conclusion has been drawn after the analysis, and suggestions have been made to the case company. After the case company analysis, the study has been developed to a general level – for all KIBS companies. And the business model framework used in this study has been slightly modified to suit better for the KIBS companies’ situation. Besides the analysis of the case company, and the recommendation has been made to the case company, there is another result, which is more on a general level, that the Rajala et al.’s business model framework (2001) has been modified as follow: firstly, the customer has been moved to the center of the framework, in order to bring people’s attention to the significance of customer; secondly, business partner has been added into the framework, in order to emphasize the importance of business partner to a company’s success

    High-mobility-group box protein 1 A box reduces development of sodium laurate-induced thromboangiitis obliterans in rats

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    ObjectiveHigh-mobility-group box protein 1 (HMGB1), as a late mediator of inflammation, plays a key role in inflammatory responses by inducing and extending the production of proinflammatory cytokines. The effect of HGMB1 in the inflammatory disease thromboangiitis obliterans (TAO) is unknown. We aimed to investigate the role of HMGB1 in sodium laurate-induced TAO in rats.MethodsMale Wistar rats were randomly divided into five groups (n = 8 each) for treatment: normal, sham-operated, TAO model, and low-dose (15 mg/kg) or high-dose (30 mg/kg) recombinant A box (rA box) infection (administered intraperitoneally once daily for 15 days). The TAO model was induced by sodium laurate and graded by gross appearance on day 15 after femoral artery injection. Histologic changes were measured by histopathology in rat femoral arteries. Plasma levels of HMGB1, thromboxane B2, 6-keto-prostaglandin F1-α, and blood cell counts and blood coagulation levels were measured. Expression of HMGB1, receptor for advanced glycation end-products (RAGE), interleukin-6, intercellular adhesion molecule-1, and vascular cell adhesion molecule-1 was assessed by immunohistochemistry and immunofluorescence, Western blot analysis, and quantitative reverse-transcription polymerase chain reaction.ResultsThe typical signs and symptoms of TAO were observed on day 15 after sodium laurate injection. The expression of HMGB1, RAGE, interleukin-6, intercellular adhesion molecule-1, and vascular cell adhesion molecule-1 was markedly increased in rat femoral arteries. Plasma levels of HMGB1 and thromboxane B2 were elevated, but the level of 6-keto-prostaglandin F1-α was decreased. Blood was in a hypercoagulable state, and prothrombin, thrombin, and activated partial thromboplastin times were all significantly shortened, whereas fibrinogen level was increased in TAO rats compared with sham-operated rats. These effects were terminated by the HMGB1 antagonist rA box.ConclusionsHMGB1 is involved in the inflammatory state in a model of TAO induced by sodium laurate in rats, probably via its receptor RAGE. As the antagonist of HMGB1, rA box can attenuate the development of TAO, which may be a potential therapeutic target for the treatment of TAO.Clinical RelevanceThromboangiitis obliterans (TAO), or Buerger disease, is a segmental nonatherosclerotic inflammatory disorder. Patients with Buerger disease have a lower quality of life because of intermittent claudication, rest pain, ulcers, and superficial thrombophlebitis. The specific etiology and pathologic mechanisms remain not elucidated. High-mobility-group box protein 1, as a late mediator of inflammation, plays a key role in inflammatory responses to tissue injury and infection by inducing and extending the production of proinflammatory cytokines. Here, we explored the role of high-mobility-group box protein 1 in rat model of TAO, discovering a new damage marker in TAO. We also investigated the unique role of recombinant A box in the prevention and treatment of TAO

    Catalytic Mechanism Investigation of Lysine-Specific Demethylase 1 (LSD1): A Computational Study

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    Lysine-specific demethylase 1 (LSD1), the first identified histone demethylase, is a flavin-dependent amine oxidase which specifically demethylates mono- or dimethylated H3K4 and H3K9 via a redox process. It participates in a broad spectrum of biological processes and is of high importance in cell proliferation, adipogenesis, spermatogenesis, chromosome segregation and embryonic development. To date, as a potential drug target for discovering anti-tumor drugs, the medical significance of LSD1 has been greatly appreciated. However, the catalytic mechanism for the rate-limiting reductive half-reaction in demethylation remains controversial. By employing a combined computational approach including molecular modeling, molecular dynamics (MD) simulations and quantum mechanics/molecular mechanics (QM/MM) calculations, the catalytic mechanism of dimethylated H3K4 demethylation by LSD1 was characterized in details. The three-dimensional (3D) model of the complex was composed of LSD1, CoREST, and histone substrate. A 30-ns MD simulation of the model highlights the pivotal role of the conserved Tyr761 and lysine-water-flavin motif in properly orienting flavin adenine dinucleotide (FAD) with respect to substrate. The synergy of the two factors effectively stabilizes the catalytic environment and facilitated the demethylation reaction. On the basis of the reasonable consistence between simulation results and available mutagenesis data, QM/MM strategy was further employed to probe the catalytic mechanism of the reductive half-reaction in demethylation. The characteristics of the demethylation pathway determined by the potential energy surface and charge distribution analysis indicates that this reaction belongs to the direct hydride transfer mechanism. Our study provides insights into the LSD1 mechanism of reductive half-reaction in demethylation and has important implications for the discovery of regulators against LSD1 enzymes

    Molecular Basis of NDM-1, a New Antibiotic Resistance Determinant

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    The New Delhi Metallo-β-lactamase (NDM-1) was first reported in 2009 in a Swedish patient. A recent study reported that Klebsiella pneumonia NDM-1 positive strain or Escherichia coli NDM-1 positive strain was highly resistant to all antibiotics tested except tigecycline and colistin. These can no longer be relied on to treat infections and therefore, NDM-1 now becomes potentially a major global health threat

    Investigation of the Acetylation Mechanism by GCN5 Histone Acetyltransferase

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    The histone acetylation of post-translational modification can be highly dynamic and play a crucial role in regulating cellular proliferation, survival, differentiation and motility. Of the enzymes that mediate post-translation modifications, the GCN5 of the histone acetyltransferase (HAT) proteins family that add acetyl groups to target lysine residues within histones, has been most extensively studied. According to the mechanism studies of GCN5 related proteins, two key processes, deprotonation and acetylation, must be involved. However, as a fundamental issue, the structure of hGCN5/AcCoA/pH3 remains elusive. Although biological experiments have proved that GCN5 mediates the acetylation process through the sequential mechanism pathway, a dynamic view of the catalytic process and the molecular basis for hGCN5/AcCoA/pH3 are still not available and none of theoretical studies has been reported to other related enzymes in HAT family. To explore the molecular basis for the catalytic mechanism, computational approaches including molecular modeling, molecular dynamic (MD) simulation and quantum mechanics/molecular mechanics (QM/MM) simulation were carried out. The initial hGCN5/AcCoA/pH3 complex structure was modeled and a reasonable snapshot was extracted from the trajectory of a 20 ns MD simulation, with considering post-MD analysis and reported experimental results. Those residues playing crucial roles in binding affinity and acetylation reaction were comprehensively investigated. It demonstrated Glu80 acted as the general base for deprotonation of Lys171 from H3. Furthermore, the two-dimensional QM/MM potential energy surface was employed to study the sequential pathway acetylation mechanism. Energy barriers of addition-elimination reaction in acetylation obtained from QM/MM calculation indicated the point of the intermediate ternary complex. Our study may provide insights into the detailed mechanism for acetylation reaction of GCN5, and has important implications for the discovery of regulators against GCN5 enzymes and related HAT family enzymes

    Black-start using battery storage and wind turbines

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    This paper discusses a black-start restoration control strategy using a battery energy storage station together with wind farms. The wind farm operates with the maximum power tracking control method, and the energy storage station adopts the V/ f control method to jointly act as the black-start resources. Soft energization is used to eliminate transformer inrush currents. A restoration sequence is designed to mitigate the transient impact by picking up critical load before connecting the wind turbines. The amount of the critical load is estimated considering the capacity and the state of charge of the energy storage station based on wind power prediction. Simulations are carried out in PSCAD/EMTDC to verify the effectiveness of the described strategy

    Invariant-Feature-Pattern-Based Form Characterization for the Measurement of Ultraprecision Freeform Surfaces

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    Ultraprecision freeform surfaces (UPFSs) are increasingly being used in advanced optical systems due to their superior optical properties. However, current research on the measurement of machined UPFSs is still hindered by lack of efficient and robust form characterization techniques which can characterize the form error of measured freeform surfaces with submicrometer accuracy. This paper presents an invariant-feature-pattern-based form characterization (IFPFC) method. IFPFC makes use of intrinsic surface features (e.g., Gaussian curvature) to map the surface into an orientation-independent feature pattern to represent the surface geometry. Surface matching and comparison are then undertaken in terms of feature pattern registration. Compared with conventional methods, the IFPFC is not only robust to the initial position of the measured surface relative to the design template but also computationally efficient since it does not involve much iteration. A series of computer simulations and actual measurement are conducted to demonstrate the performance and the validity of the IFPFC method in the measurement and characterization of UPFSs with submicrometer form accuracy.Department of Industrial and Systems Engineerin

    Aorto-left ventricular tunnel with anomalous origin of right coronary artery and bicuspid aortic valve: a case report

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    Abstract Background Aorto-left ventricular tunnel (ALVT) is a rare congenital extracardiac channel that connects the ascending aorta to the left ventricle. To our knowledge, no case has been thus far reported as ALVT with both anomalous origin of right coronary artery (AORCA) and bicuspid aortic valve (BAV). Case presentation We reported a case of a 5-year-old female diagnosed as ALVT with accompanying AORCA and BAV which had been previously misdiagnosed as aortic regurgitation (AR) triggered by BAV. Additionally, a special modality of ALVT was confirmed in this case during the surgery in which the tunnel was formed by the separation between the roots of two aortic leaflets during the diastolic period. Conclusions ALVT with both AORCA and BAV is clinically uncommon and the aberrant tunnel in ALVT can be formed by the gap between the roots of two aortic leaflets. Besides, ALVT with BAV might easily lead to an inaccurate diagnose as aortic regurgitation caused by BAV. Cardiac surgeons should be alerted for differential diagnosis of ALVT with BAV and isolated bicuspid aortic valve (BAV) causing aortic regurgitation (AR)
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