Packing While Traveling: Mixed Integer Programming for a Class of Nonlinear Knapsack Problems

Packing and vehicle routing problems play an important role in the area of supply chain management. In this paper, we introduce a non-linear knapsack problem that occurs when packing items along a fixed route and taking into account travel time. We investigate constrained and unconstrained versions of the problem and show that both are NP-hard. In order to solve the problems, we provide a pre-processing scheme as well as exact and approximate mixed integer programming (MIP) solutions. Our experimental results show the effectiveness of the MIP solutions and in particular point out that the approximate MIP approach often leads to near optimal results within far less computation time than the exact approach

Stabilisation of the Fc Fragment of Human IgG1 by Engineered Intradomain Disulfide Bonds

We report the stabilization of the human IgG1 Fc fragment by engineered intradomain disulfide bonds. One of these bonds, which connects the N-terminus of the CH3 domain with the F-strand, led to an increase of the melting temperature of this domain by 10°C as compared to the CH3 domain in the context of the wild-type Fc region. Another engineered disulfide bond, which connects the BC loop of the CH3 domain with the D-strand, resulted in an increase of Tm of 5°C. Combined in one molecule, both intradomain disulfide bonds led to an increase of the Tm of about 15°C. All of these mutations had no impact on the thermal stability of the CH2 domain. Importantly, the binding of neonatal Fc receptor was also not influenced by the mutations. Overall, the stabilized CH3 domains described in this report provide an excellent basic scaffold for the engineering of Fc fragments for antigen-binding or other desired additional or improved properties. Additionally, we have introduced the intradomain disulfide bonds into an IgG Fc fragment engineered in C-terminal loops of the CH3 domain for binding to Her2/neu, and observed an increase of the Tm of the CH3 domain for 7.5°C for CysP4, 15.5°C for CysP2 and 19°C for the CysP2 and CysP4 disulfide bonds combined in one molecule

OVERHEATED SECURITY? The Securitisation of Climate Change and the Governmentalisation of Security

Since the mid-2000s, climate change has become one of the defining security issues in political as well as academic debates and amongst others has repeatedly been discussed in the UN Security Council and countless high level government reports in various countries. Beyond the question whether the characterisation as ‘security issue’ is backed up by any robust empirical findings, this begs the question whether the ‘securitisation’ of climate change itself has had tangible political consequences. Moreover, within this research area there is still a lively discussion about which security conceptions apply, how to conceptualise (successful) securitisation and whether it is a (politically and normatively) desirable approach to deal with climate change. The aim of this dissertation is to shed light on these issues and particularly to contribute to a more thorough understanding of different forms or ‘discourses’ of securitisation and their political effects on a theoretical and empirical level. Theoretically, it conceptualises securitisation as resting on different forms of power, which are derived from Michel Foucault’s governmentality lectures. The main argument is that this framework allows me to better capture the ambiguous and diverse variants of securitisation and the ever-changing concept of security as well as to come to a more thorough understanding of the political consequences and powerful effects of constructing issues in terms of security. Empirically, the thesis looks at three country cases, namely the United States, Germany and Mexico. This comparative angle allows me to go beyond the existing literature on the securitisation of climate change that mostly looks at the global level, and to come to a more comprehensive and detailed understanding of different climate security discourses and their political consequences. Concerning the main results, the thesis finds that climate change has indeed been securitised very differently in the three countries and thus has facilitated diverse political consequences. These range from an incorporation of climate change into the defence sector in the US, the legitimisation of far-reaching climate policies in Germany, to the integration of climate change into several civil protection and agricultural insurance schemes in Mexico. Moreover, resting on different forms of power, the securitisation of climate change has played a key role in constructing specific actors and forms of knowledge as legitimate as well as in shaping certain identities in the face of the dangers of climate change. From a normative perspective, neither of these political consequences is purely good or bad but highly ambiguous and necessitates a careful, contextual assessment

Using resource modelling to inform decision making and service planning: the case of colorectal cancer screening in Ireland

Background - Organised colorectal cancer screening is likely to be cost-effective, but cost-effectiveness results alone may not help policy makers to make decisions about programme feasibility or service providers to plan programme delivery. For these purposes, estimates of the impact on the health services of actually introducing screening in the target population would be helpful. However, these types of analyses are rarely reported. As an illustration of such an approach, we estimated annual health service resource requirements and health outcomes over the first decade of a population-based colorectal cancer screening programme in Ireland. Methods - A Markov state-transition model of colorectal neoplasia natural history was used. Three core screening scenarios were considered: (a) flexible sigmoidoscopy (FSIG) once at age 60, (b) biennial guaiac-based faecal occult blood tests (gFOBT) at 55–74 years, and (c) biennial faecal immunochemical tests (FIT) at 55–74 years. Three alternative FIT roll-out scenarios were also investigated relating to age-restricted screening (55–64 years) and staggered age-based roll-out across the 55–74 age group. Parameter estimates were derived from literature review, existing screening programmes, and expert opinion. Results were expressed in relation to the 2008 population (4.4 million people, of whom 700,800 were aged 55–74). Results - FIT-based screening would deliver the greatest health benefits, averting 164 colorectal cancer cases and 272 deaths in year 10 of the programme. Capacity would be required for 11,095-14,820 diagnostic and surveillance colonoscopies annually, compared to 381–1,053 with FSIG-based, and 967–1,300 with gFOBT-based, screening. With FIT, in year 10, these colonoscopies would result in 62 hospital admissions for abdominal bleeding, 27 bowel perforations and one death. Resource requirements for pathology, diagnostic radiology, radiotherapy and colorectal resection were highest for FIT. Estimates depended on screening uptake. Alternative FIT roll-out scenarios had lower resource requirements. Conclusions - While FIT-based screening would quite quickly generate attractive health outcomes, it has heavy resource requirements. These could impact on the feasibility of a programme based on this screening modality. Staggered age-based roll-out would allow time to increase endoscopy capacity to meet programme requirements. Resource modelling of this type complements conventional cost-effectiveness analyses and can help inform policy making and service planning