1,889 research outputs found

    Systematic prioritization of considerations in making offshore software development outsourcing decisions

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    Thesis (M. Eng.)--Massachusetts Institute of Technology, Dept. of Electrical Engineering and Computer Science, 2005.Includes bibliographical references (leaves 43-45).Offshore outsourcing of software development projects has become increasingly prevalent over the past decade. In order to avoid potential pitfalls in outsourcing, companies must carefully select who to outsource to. Although general guidelines exist for those companies to consult, they are not customizable to the unique needs of each company and project. By assessing the type of a company's outsourceable project and its in-house capabilities regarding the project, the main outsourcing goal of the company is first determined. Depending on the goal, the essential issues to be considered in making outsourcing decisions are then prioritized systematically. Case studies have been conducted to support the set prioritization patterns, followed by an examination of current limitations and possible future work.by Bo S. Kim.M.Eng

    A novel regulator of the p53-mediated mitochondrial apoptotic pathway

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    The p53 tumor suppressor protein induces apoptosis in response to genotoxic and environmental stress. Recent studies have revealed the existence of a transcription-independent mitochondrial p53 apoptosis pathway, however the mechanism regulating p53 translocation to mitochondria and subsequent initiation of apoptosis was not known. Here, we show that Tid1, also known as mtHsp40 or Dnaja3, interacts with p53 and directs its translocation to mitochondria in cells exposed to hypoxia. Overexpression of Tid1 in tumor cells promoted mitochondrial localization of both wildtype and mutant forms of p53 and was able to restore the pro-apoptotic activity of mutant p53 proteins that were otherwise unable to induce apoptosis. Tid1's mitochondrial signal sequence and DnaJ domain were both required for the movement of the p53-Tid1 complex from the cytosol to the mitochondria. Our findings establish Tid1 as a novel regulator of p53 localization and apoptotic function

    Electrogenic transport and K(+) ion channel expression by the human endolymphatic sac epithelium.

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    The endolymphatic sac (ES) is a cystic organ that is a part of the inner ear and is connected to the cochlea and vestibule. The ES is thought to be involved in inner ear ion homeostasis and fluid volume regulation for the maintenance of hearing and balance function. Many ion channels, transporters, and exchangers have been identified in the ES luminal epithelium, mainly in animal studies, but there has been no functional study investigating ion transport using human ES tissue. We designed the first functional experiments on electrogenic transport in human ES and investigated the contribution of K(+) channels in the electrogenic transport, which has been rarely identified, even in animal studies, using electrophysiological/pharmacological and molecular biological methods. As a result, we identified functional and molecular evidence for the essential participation of K(+) channels in the electrogenic transport of human ES epithelium. The identified K(+) channels involved in the electrogenic transport were KCNN2, KCNJ14, KCNK2, and KCNK6, and the K(+) transports via those channels are thought to play an important role in the maintenance of the unique ionic milieu of the inner ear fluid

    Robust network calibration and therapy design in systems biology

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    Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Electrical Engineering and Computer Science, 2010.Cataloged from PDF version of thesis.Includes bibliographical references (p. 115-123).Mathematical modeling of biological networks is under active research, receiving attention for its ability to quantitatively represent the modeler's systems-level understanding of network functionalities. Computational methods that enhance the usefulness of mathematical models are thus being increasingly sought after, as they face a variety of difficulties that originate from limitations in model accuracy and experimental precision. This thesis explores robust optimization as a tool to counter the effects of these uncertainty-based difficulties in calibrating biological network models and in designing protocols for cancer immunotherapy. The robust approach to network calibration and therapy design aims to account for the worst-case uncertainty scenario that could threaten successful determination of network parameters or therapeutic protocols, by explicitly identifying and sampling the region of potential uncertainties corresponding to worst-case. Through designating individual numerical ranges that uncertain model parameters are each expected to lie within, the region of uncertainties is defined as a hypercube that encompasses a particular uncertainty range along each of its dimensions. For investigating its applicability to parameter estimation, the performance of the optimization method that embodies this robust approach is examined in the context of a model of a unit belonging to the mitogen-activated protein kinase pathway. For its significance in therapeutic design, the method is applied to both a canonical mathematical model of the tumor-immune system and a model specific to treating superficial bladder cancer with Bacillus Calmette-Guirin, which have both been selected to examine the plausibility of applying the method to either discrete-dose or continuous-dose administrations of immunotherapeutic agents. The robust optimization method is evaluated against a standard optimization method by comparing the relative robustness of their respective estimated parameters or designed therapies. Further analysis of the results obtained using the robust method points to properties and limitations, and in turn directions for improvement, of existing models and design frameworks for applying the robust method to network calibration and protocol design. An alternative mathematical formulation to solving the worst-case optimization problem is also studied, one that replaces the sampling process of the previous method with a linearization of the objective function's parameter space over the region of uncertainties. This formulation's relative computational efficiency additionally gives rise to a novel approach to experimental guidance directed at improving modeling efforts under uncertainties, which may potentially further fuel the advancement of quantitative systems biological research.by Bo S. Kim.Ph.D

    Anti-oxidative and anti-neuroinflammatory effects of ethyl acetate extract fractions of Suaeda asparagoides MIq

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    Purpose: To evaluate the in vitro antioxidant and anti-neuroinflammatory effects of Suaeda asparagoides ethylacetate extract (SAE) in lipopolysaccharide (LPS)-stimulated BV-2 microglial cells.Methods: The antioxidative activity of SAE was evaluated by measuring 1, 1-diphenyl-2-picryl-hydrazyl (DPPH) radical scavenging activity  spectrometrometrically. Cell viability was evaluated by 3-(4, 5- dimethylthiazol-2-yl)-2, 5- diphenyl-tetrazolium bromide (MTT) assay, while LPS-stimulated BV-2 microglia were used to study the expression and production of inflammatory mediators, including nitric oxide (NO), inducible NO synthase (iNOS) and tumor necrosis alpha (TNF-α).Results: Pretreatment with SAE prior to LPS treatment significantly inhibited excessive production of NO (p < 0.001 at 20, 40, 80 and 100 μg/mL) in a dose-dependent manner, and was associated with down-regulation of expression of inducible nitric oxide synthase (iNOS). SAE also suppressed the LPSinduced increase in TNF-α level (p < 0.01at concentrations of 40 and 80 μg/mL) in BV-2 cells. Furthermore, DPPH-generated free radicals were inhibited by SAE in a concentration-dependent manner.Conclusion: These results indicate that SAE possesses strong anti-oxidant properties, and inhibits excessive production of pro-inflammatory mediators, including NO, iNOS and TNF-α, in LPS-stimulated BV-2 cellsKeywords: Suaeda asparagoides, DPPH, Anti-inflammatory activity, Microglial cells, iNOS, TNF-

    The Influence Of Job Insecurity On Career Commitment And Attitude In Multinational Corporations

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    As the perception of lifelong work shifts into lifelong career in the job insecurity market, the career development of employees through professional and competitive career management has become more important than being loyal to a lifelong work. Furthermore, in the case of multinational corporations, such as differentiation from the head office policy, cultural differences in labor relations, and the liquidity of business withdrawal, such a feature has a higher possibility of job insecurity than general companies. Therefore, the purpose of this study is to verify empirically how job insecurity influences career commitment and career attitude through individual, job and career characteristics as intermediation with the members of multinational corporations as objectives. For this purpose, a total of 366 questionnaire data that targeted 27 multinational corporations were collected and analyzed. The result shows that the job insecurity of multinational corporations affects individual characteristic rather than job or career characteristic, and it is confirmed that individual characteristic has an effect on career commitment and career attitude. In the end, multinational corporations, unlike ordinary domestic companies, need active organizational career development program that corresponds to an open corporate culture as well as innovative and open systems and policies that balance both internal and external networking activities in terms of human resource management of corporations

    Lymphangiography to treat postoperative lymphatic leakage: a technical review.

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    In addition to imaging the lymphatics and detecting various types of lymphatic leakage, lymphangiography is a therapeutic option for patients with chylothorax, chylous ascites, and lymphatic fistula. Percutaneous thoracic duct embolization, transabdominal catheterization of the cisterna chyli or thoracic duct, and subsequent embolization of the thoracic duct is an alternative to surgical ligation of the thoracic duct. In this pictorial review, we present the detailed technique, clinical applications, and complications of lymphangiography and thoracic duct embolization

    Observation of trapped-modes excited in double-layered symmetric electric ring resonators

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    We report on experimental observations of trapped-mode resonances in double-layered symmetric electric ring resonators separated by dielectric inserts. The resulting metamaterial introduces trapped-mode resonances that were thought to be produced only by asymmetric metamaterial unit cells. Experimental verification of the newly observed trapped modes, along with the analysis of the stacked metamaterial geometry reported in this paper, opens an alternative way of forming sharp resonances in a symmetric metamaterial structure extended in all three dimensions.open9
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