A combined model reduction algorithm for controlled biochemical systems

Background: Systems Biology continues to produce increasingly large models of complex biochemical reaction networks. In applications requiring, for example, parameter estimation, the use of agent-based modelling approaches, or real-time simulation, this growing model complexity can present a significant hurdle. Often, however, not all portions of a model are of equal interest in a given setting. In such situations methods of model reduction offer one possible approach for addressing the issue of complexity by seeking to eliminate those portions of a pathway that can be shown to have the least effect upon the properties of interest. Methods: In this paper a model reduction algorithm bringing together the complementary aspects of proper lumping and empirical balanced truncation is presented. Additional contributions include the development of a criterion for the selection of state-variable elimination via conservation analysis and use of an ‘averaged’ lumping inverse. This combined algorithm is highly automatable and of particular applicability in the context of ‘controlled’ biochemical networks. Results: The algorithm is demonstrated here via application to two examples; an 11 dimensional model of bacterial chemotaxis in Escherichia coli and a 99 dimensional model of extracellular regulatory kinase activation (ERK) mediated via the epidermal growth factor (EGF) and nerve growth factor (NGF) receptor pathways. In the case of the chemotaxis model the algorithm was able to reduce the model to 2 state-variables producing a maximal relative error between the dynamics of the original and reduced models of only 2.8% whilst yielding a 26 fold speed up in simulation time. For the ERK activation model the algorithm was able to reduce the system to 7 state-variables, incurring a maximal relative error of 4.8%, and producing an approximately 10 fold speed up in the rate of simulation. Indices of controllability and observability are additionally developed and demonstrated throughout the paper. These provide insight into the relative importance of individual reactants in mediating a biochemical system’s input-output response even for highly complex networks. Conclusions: Through application, this paper demonstrates that combined model reduction methods can produce a significant simplification of complex Systems Biology models whilst retaining a high degree of predictive accuracy. In particular, it is shown that by combining the methods of proper lumping and empirical balanced truncation it is often possible to produce more accurate reductions than can be obtained by the use of either method in isolation

Methods of model reduction for large-scale biological systems: a survey of current methods and trends

Complex models of biochemical reaction systems have become increasingly common in the systems biology literature. The complexity of such models can present a number of obstacles for their practical use, often making problems difficult to intuit or computationally intractable. Methods of model reduction can be employed to alleviate the issue of complexity by seeking to eliminate those portions of a reaction network that have little or no effect upon the outcomes of interest, hence yielding simplified systems that retain an accurate predictive capacity. This review paper seeks to provide a brief overview of a range of such methods and their application in the context of biochemical reaction network models. To achieve this, we provide a brief mathematical account of the main methods including timescale exploitation approaches, reduction via sensitivity analysis, optimisation methods, lumping, and singular value decomposition-based approaches. Methods are reviewed in the context of large-scale systems biology type models, and future areas of research are briefly discussed

Webbaserad realtidsuppföljdkvalitetsundersökning

Swedish school has for the last decades been using quality management as a method for improvement. Quality management is an enormous work and the whole school staff needs to be involved. The management consists of several parts like planning, surveys and interviews, analysis of the replies and setting up new goals. Parents, children and teachers are nowadays accustomed with quality surveys. The last few years these quality surveys have been computerized, but they still look almost the same, using little interaction with the respondent.I have had the opportunity to work with the company KMF Ventures, which has a vision that entails a more interactive web survey. This web survey gives both the school board and the pupils a possibility to compare their school with others. Hopefully this make them more interested in responding. The web survey is always open and the pupils can respond whenever they change opinion.This report describes the development process of the quality control tool for the web survey. The web tool has furthermore been evaluated in two Swedish gymnasium schools. Interviews have been held with teachers, school board and pupils. The purpose was to see how their quality management system works and how it has been changed when they starts to use this quality control tool. I also wanted to see how the schools handle problems with for example teachers.The questions in the web survey are few but they look practically the same as the ones already being used by the schools. They questions differ however from other surveys in the way it use only “yes” and “no” as responses.The quality web tool indicated that there were some problems in the schools. The lack of experience made however the schools to take little notice, even less to take action. This shows that education and planning of a new quality control tool is of great importance. The comparison option was nevertheless highly valued. This quality control tool could have a future, but it requires significant improvements. The company needs for example to consider the possibilities of a more well-known method for surveys. Most important is though that the company helps the school with the planning and the introduction of the new quality survey

Optimering av kylsystem för laddluft, Bandvagn S10

Validerat; 20101217 (root

Sam- och särundervisning i ämnet idrott och hälsa : Vad tycker idrottslärarna?

Syftet med arbetet är att undersöka idrottslärares tankar kring sam- och särundervisning samt att undersöka vilken undervisningsmetod som idrottslärarna föredrar att arbeta med. Min frågeställning är: Vilken undervisningsmetod är att föredra i ämnet idrott och hälsa anser lärarna? Vilka fördelar och nackdelar finns det med sam- respektive särundervisning? Gynnas flickor eller pojkar beroende på undervisningsmetoden? För att besvara min frågeställning och få fram idrottslärares åsikter i frågan gjorde jag kvalitativa intervjuer med fem idrottslärare i olika kön och ålder. Resultatet av undersökningen visar att fyra av idrottslärarna hade varit med om både sam- och särundervisning varav tre använde sig av samundervisning och två av särundervisning nu. Fyra av idrottslärarna föredrog att använda sig av samundervisning då de ansåg att den undervisningsmetoden hade flest positiva effekter. Särundervisning gynnade mest de fysiskt svagare flickorna. Nivågruppering var också en undervisningsmetod som många av idrottslärarna använde sig av vid vissa moment i undervisningen

The effect of Cutibacterium acnes on macrophage production of PD-L1

Prostatacancer är den vanligaste cancerformen hos män i Sverige, och det är även den cancerform som flest män dör utav. Detta till trots så är mekanismerna bakom canceretiologin till stor del okända. Uppskattningsvis 20% av alla canceruppkomster i människor tros vara länkade till infektioner från patogener och de inflammationer som de orsakar. Tidigare studier har visat indikationer på att kronisk inflammation av prostatan kan hjälpa tumörer att undvika immunförsvaret. Bakterien Cutibacterium acnes förekommer i stor utsträckning i prostatavävnad hos patienter som lider av prostatacancer vilket kan peka på en länk mellan mikroorganismen och cancerformen. Tumörassocierade makrofager kan producera immunhämmande proteiner, däribland liganden PD-L1, ett protein som kan hjälpa tumörcellerna att undgå immunförsvaret. Studien ämnade därför att undersöka huruvida makrofager som infekterats med typ I eller typ II C. acnes producerar en högre mängd av PD-L1 än obehandlade makrofager och i detta syfte utfördes ett ELISA-test som bestämde koncentrationen av PD-L1 i odlingsmediumet. Genom en statistisk analys konstaterades att makrofager som infekterats med bakterien ökade produktionen av PD-L1 jämfört med obehandlade makrofager. Resultatet av studien visar indikationer på att C. acnes kan spela en roll i spridningen av tumörceller i kroppen, dock krävs vidare studier för att bekräfta hypotesen.Prostate cancer is the most common form of cancer among men in Sweden, and the form of cancer that most men die from. In spite of this, the mechanisms behind the etiology of the cancer are largely unknown. Approximately 20% of all cancer etiologies are believed to be linked to infection by pathogens, and the inflammatory response they cause within the body. Earlier studies have shown indications that chronic inflammation of the prostate might create conditions that are favourable for the tumour cells. The bacterium Cutibacterium acnes is prevalent in prostate tissue from patients suffering from prostate cancer, which might indicate a link between the microorganism and this form of cancer. Tumour associated macrophages produce immunosuppressive proteins, such as the ligand PD-L1, a protein that might provide immunoevasive qualities for the tumour cells. The aim of the study was to examine whether macrophages that have been infected with either type I or type II C. acnes would produce a greater amount of PD-L1 than untreated macrophages. For this purpose, an ELISA test was performed to determine the concentrations of PD-L1 in the culture media. I found that macrophages that had been infected with the bacterium produced greater amounts of PD-L1 than untreated macrophages. The result of this study shows some indication that C. acnes could play a role in the proliferation of tumour cells and thus the spread of cancer through immunosuppresive mechanisms, although further studies are needed to confirm this hypothesis

Evaluating LOAd703 in combination with chemotherapeutic agents in ovarian cancer

Ovarian cancer is a disease with a high rate of mortality where the need for novel treatments will increase in the near future as older and populous generations reach the age where the cancer is usually diagnosed. Once treated, ovarian cancer tends to recur and display a newfound resistance against the platinum-based chemotherapeutic drugs that are used to treat the disease. Therefore, devising new methods of treatment is of utmost importance. Treatment with oncolytic viruses like LOAd703 offers an alternative treatment option that is more specific, causes immunogenic cell death in tumor cells, can stimulate the patient’s own immune system into fighting the cancer, and also has the potential to induce long term immune memory. In this project, the oncolytic and immunogenic capacity of LOAd703 in three different ovarian cancer cell lines was tested in conjunction with the standard-of-care chemotherapeutical drugs paclitaxel, cisplatin and carboplatin. The chemotherapy did not inhibit the replication, transgene expression or oncolysis of the LOAd703 virus. LOAd703 was able to effectively induce oncolysis in all three cell lines. The oncolytic capacity was generally increased when combined with chemotherapeutics. In cells resistant to chemotherapeutics, combination therapy with LOAd703 increased the killing capacity. While combination therapy proved effective, it did leave behind a small population of tumor cells that appeared to be resistant to both chemotherapy and viral oncolysis but longer culturing times may be tested to evaluate if complete killing will occur or if it is a primary resistance to these treatments in the cell lines. Further, if there is resistance to oncolysis or chemotherapy-mediated killing, employing tumor-immune cell co-cultures or in vivo studies might be necessary in order to assess whether the immunostimulatory effects of LOAd703 will lead to a complete eradication of the remaining tumor cells. The treatments also caused an increase in the expression of certain cell surface markers, like PD-L1 and CD262, which might open the door for future trials combining chemotherapy and LOAd703 with anti-PD-L1 inhibitors or soluble TRAIL

Strå - Folkets hus

Strå - folkets hus in Alberga is a place for community, culture and wildlife. Its located in the verge between Albergas more densely populated area and the  sparsely populated fields of the rural landscape. In previous project we saw Alberga answer the increasing population by 2030 by develop what we come to name as "Cluster-village", to build new with inspiration and with similar typology as what already is. Every cluster have their own agricultural land for 100% self-sufficiency of vegan diet, increasing the areas resilience. Strå - folkets hus constitutes an important part by being the connecting link between the local community of Alberga and the areas small-scale farming, thus the placing and the program. The building have several parts to play, research centre to develop ecological and long-term small-scale farming in the northern climate, community centre for the locals, storage and sharing knowledge for the Cluster-villages, but perhaps most importantly accommodates pollinators. The roof of the building is made out of reed, a local and ecologically friendly material, which even creates shelter for one of earth most vital and delicate creature, the pollinators. As the area is surrounded by scenic landscape, rich in wildlife and community, Strå - folkets hus serves as the link between farming and culture.

Strå - Folkets hus

Strå - folkets hus in Alberga is a place for community, culture and wildlife. Its located in the verge between Albergas more densely populated area and the  sparsely populated fields of the rural landscape. In previous project we saw Alberga answer the increasing population by 2030 by develop what we come to name as "Cluster-village", to build new with inspiration and with similar typology as what already is. Every cluster have their own agricultural land for 100% self-sufficiency of vegan diet, increasing the areas resilience. Strå - folkets hus constitutes an important part by being the connecting link between the local community of Alberga and the areas small-scale farming, thus the placing and the program. The building have several parts to play, research centre to develop ecological and long-term small-scale farming in the northern climate, community centre for the locals, storage and sharing knowledge for the Cluster-villages, but perhaps most importantly accommodates pollinators. The roof of the building is made out of reed, a local and ecologically friendly material, which even creates shelter for one of earth most vital and delicate creature, the pollinators. As the area is surrounded by scenic landscape, rich in wildlife and community, Strå - folkets hus serves as the link between farming and culture.