C/EBPβ isoforms and the regulation of metabolism:A fine balance between health and disease

Calorie inname en dieet samenstellingen reguleren de eiwit productie en functionaliteit in de cel en oefenen hierdoor een directe invloed uit op de gezondheid en het metabolisme van organismen. Afwijkingen in het metabolisme en verhoogde calorie-inname kunnen leiden tot het ontstaan van metabole ziekten zoals type 2 diabetes en obesitas. Voorheen zijn verschillende factoren geïdentificeerd welke reageren op dieet samenstellingen en calorie-inname en hierdoor een cellulaire respons in gang zetten. In dit proefschrift beschrijven we dat C/EBPβ-LIP een belangrijke factor is die aangestuurd wordt door diëten. C/EBPβ-LIP is een DNA-binding eiwit en vermindert de productie van DNA gecodeerde RNAs en eiwitten om de cellulaire functies te reguleren. Muizen met verminderde hoeveelheden LIP zijn metabool gezonder dan muizen met normale LIP hoeveelheden onder dezelfde diëtaire omstandigheden. Verder beschrijven we hoe verhoogde hoeveelheden LIP resulteert in een metabolisme die vergelijkbaar is met het metabolisme van kanker cellen. We hebben in dit proefschrift LIP geïdentificeerd als factor die gereguleerd wordt door het dieet en de verwerking van voedingsstoffen in de cel veranderd. Om deze reden dragen we LIP voor als belangrijke regulator van lichaamsfuncties, en speculeren we dat een vermindering van LIP door farmacologische inhibitie wellicht kan bijdragen aan de behandeling van metabole ziekten en kanker

Taxonomy of Technological IT Outsourcing Risks: Support for Risk Identification and Quantification

The past decade has seen an increasing interest in IT outsourcing as it promises companies many economic benefits. In recent years, IT paradigms, such as Software-as-a-Service or Cloud Computing using third-party services, are increasingly adopted. Current studies show that IT security and data privacy are the dominant factors affecting the perceived risk of IT outsourcing. Therefore, we explicitly focus on determining the technological risks related to IT security and quality of service characteristics associated with IT outsourcing. We conducted an extensive literature review, and thoroughly document the process in order to reach high validity and reliability. 149 papers have been evaluated based on a review of the whole content and out of the finally relevant 68 papers, we extracted 757 risk items. Using a successive refinement approach, which involved reduction of similar items and iterative re-grouping, we establish a taxonomy with nine risk categories for the final 70 technological risk items. Moreover, we describe how the taxonomy can be used to support the first two phases of the IT risk management process: risk identification and quantification. Therefore, for each item, we give parameters relevant for using them in an existing mathematical risk quantification model

A Treaty on Enforcing Human Rights Against Business: Closing the Loophole or Getting Stuck in a Loop?

This Article takes a human rights law perspective on the issue of enforcing corporate social responsibility. While corporations receive a variety of rights under international law, they do not equally hold a corresponding set of duties. The Article assesses the merits and shortcomings of existing initiatives to bridge this gap, in particular the Special Representative to the Secretary-General\u27s (legally nonbinding) Framework and Guiding Principles, as well as the most recent initiative at the United Nations Human Rights Council on developing a (legally binding) treaty on business and human rights. While emphasizing that existing legal frameworks-such as human rights law, international criminal law, and international investment law-do not suffice to close this loophole (of corporations being rights bearing but not rights bound), the Article remains equally skeptical about the prospects for a new legally binding treaty. Even if such a treaty were realized, it remains largely unclear how and by which bodies such a treaty would be enforced toward corporations. The authors suggest concentrating efforts on improving the enforceability of existing standards under the Framework and Guiding Principles rather than striving for a new treaty, and to do so on the international, but even more on the national, level

Cell culture medium formulation and its implications in cancer metabolism

Historic cell culture media were designed to ensure continuous cancer cell proliferation in vitro. However, their composition does not recapitulate the nutritional environment of the tumor. Recent studies show that novel media formulations alleviate the nonphysiological constraints imposed by historic media, and lead to cell culture results that are more relevant to tumor metabolism

Quantifying Risks in Service Networks: Using Probability Distributions for the Evaluation of Optimal Security Levels

The increasing costs and frequency of security incidents require organizations to apply proper IT risk management. At the same time, the expanding usage of Service-oriented Architectures fosters software systems composed of cross-linked services. Therefore, it is important to develop risk management methods for these composite systems. In this paper, we present a straightforward model that can be used to quantify the risks related to service networks. Based on the probability distribution of the costs which are related to risks, it is possible to make proper investment choices using individual risk preferences. The attractiveness of investment alternatives and different levels of security can be measured with various characteristics like the expected value of the costs, the Value-at-Risk or more complex utility functions. Through performance evaluations we show that our model can be used to calculate the costs’ probability density function for large scale networks in a very efficient way. Furthermore, we demonstrate the application of the model and the algorithms with the help of a concrete application scenario. As a result, we improve IT risk management by proposing a model which supports decision makers in comparing alternative service scenarios and alternative security investments in order to find the optimal level of IT security