Use of the R-group descriptor for alignment-free QSAR

An R-group descriptor characterises the distribution of some atom-based property, such as elemental type or partial atomic charge, at increasing numbers of bonds distant from the point of substitution on a parent ring system. Application of Partial Least Squares (PLS) to datasets for which bioactivity data and R-group descriptor information are available is shown to provide an effective way of generating QSAR models with a high level of predictive ability. The resulting models are competitive with the models produced by established QSAR approaches, are readily interpretable in structural terms, and are shown to be of value in the optimisation of a lead series

ChemmineR: a compound mining framework for R

Motivation: Software applications for structural similarity searching and clustering of small molecules play an important role in drug discovery and chemical genomics. Here, we present the first open-source compound mining framework for the popularstatistical programming environment R. The integration with a powerful statistical environment maximizes the flexibility, expandability and programmability of the provided analysis functions

Visual and computational analysis of structure-activity relationships in high-throughput screening data

Novel analytic methods are required to assimilate the large volumes of structural and bioassay data generated by combinatorial chemistry and high-throughput screening programmes in the pharmaceutical and agrochemical industries. This paper reviews recent work in visualisation and data mining that can be used to develop structure-activity relationships from such chemical/biological datasets

Greedy and linear ensembles of machine learning methods outperform single approaches for QSPR regression problems

The application of Machine Learning to cheminformatics is a large and active field of research, but there exist few papers which discuss whether ensembles of different Machine Learning methods can improve upon the performance of their component methodologies. Here we investigated a variety of methods, including kernel-based, tree, linear, neural networks, and both greedy and linear ensemble methods. These were all tested against a standardised methodology for regression with data relevant to the pharmaceutical development process. Thinvestigation focused on QSPR problems within drug-like chemical space. We aimed to investigate which methods perform best, and how the ‘wisdom of crowds’ principle can be applied to ensemble predictors. It was found that no single method performs best for all problems, but that a dynamic, well-structured ensemble predictor would perform very well across the board, usually providing an improvement in performance over the best single method. Its use of weighting factors allows the greedy ensemble to acquire a bigger contribution from the better performing models, and this helps the greedy ensemble generally to outperform the simpler linear ensemble. Choice of data pre-processing methodology was found to be crucial to performance of each method too.PostprintPeer reviewe

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Reserve replacement in the oil and gas industry -A study on cost differences

Background and the question at issue: When attempting to increment oil and gas reserves, an oil and gas company typically has two possibilities, either to prospect and develop reserves or to acquire reserves through a takeover of another company with proved reserves. In this thesis, the reader will find an approximated answer to the question at issue about which of these alternatives is the most cost effective. Purpose: The thesis was written with the intent to fill some of the holes in the academic literature regarding the cost effectiveness, related to the increment of oil and gas reserves. The paper also contains a discussion about the determents of value and costs in the oil and gas industry, written with the intention to contribute to the illumination of the economical dynamics of the industry. Delimitations: Some generalizations have been made in this thesis in order to increment the transparency and perspicuousness of the study. Methodology: This thesis was enabled by a thorough study of relevant academic research and empirical data, e.g. annual reports and press releases. The costs and outcomes of exploration activities between the years 2009-2013 was gathered from the ten largest oil and gas companies, according to the market capitalization per 2015-04-15, and compared to eight acquisitions that where considered to be a appropriate. Conclusions: The findings of this study indicate that, from a strictly economic perspective, that the alternative to prospect and develop oil and gas reserves is the most cost effective way to increment reserves, although the findings are not statistically significant. Possible stakeholders: This thesis should be interesting to anyone who takes particular interest in the oil and gas industry

Försvarsmaktens befälssystem – en struktur i ständig förändring : Försvarsmaktens implementering av ett flerbefälssystem

Försvarsmaktens organisation har ett behov av ständig förändring för att kunna hantera de yttre och inre påverkansfaktorer som följer av det säkerhetspolitiska läget, samhällsutvecklingen och den teknologiska utvecklingen. Vi har genom en hermeneutisk kvalitativ studie undersökt hur organisationen förändrats genom implementeringen av ett flerbefälssystem. Vi har försökt att identifiera de drivkrafter som har legat bakom förändringarna och förstå de beslut som har fattats. Våra primärkällor har utgjorts av människor i organisationen; befattningshavare med olika roller, på olika nivåer och med olika bakgrund. Våra sekundärkällor har framförallt bestått av officiella dokument och skrivelser som organisationen nyttjat under implementeringen.Vi har analyserat inhämtad data mot flera olika organisationsteorier och kommit fram till att den långa sekventiella implementeringen haft olika fokus i olika sekvenser. Utmaningen för Försvarsmakten har varit att skapa balans mellan organisationens strukturella och individens mänskliga behov samt att kommunicera argument och incitament för organisations-förändringen. Maktpersoner i organisationen har löpande påverkat processen och systemdesignen har självmuterat från initial konfiguration till den beskrivning som finns idag.Försvarsmaktens strukturella slutinförande av Trebefälssystemet har orsakat suboptimering av implementeringen i dess sista sekvens, och motverkat möjligheterna för främst specialist-officersskrået att utvecklas mot en egen profession; skrået är fortsatt styvmoderligt behandlat av organisationen, och det finns en risk för en utveckling mot segregation och oönskade kulturer. Ytterst har detta haft en negativ effekt på den operativa förmågan.Överbefälhavarens beslut om slutligt införande var ett nödvändigt beslut för att forma den struktur som borde ha intagits för många år sedan, dock hade organisationens behov bättre kunnat omhändertas om även individens behov hade tillgodosetts.Försvarsmakten har nu ett enda system där samtligt befäl är inordnade, men arbetet är inte slutfört. Det finns fortfarande en del problemområden att ta tag i, men samtidigt också gyllene chanser att fortsätta utvecklingen av systemet för att nå än större effekt än det har idag.The Swedish Armed Forces has a need for constant change in order to be able to handle the external and internal influencing factors that result from the changing security policy situation, societal development and technological development. Through a hermeneutic qualitative study, we have investigated how the organization has changed through the implementation of a multi-command system. We have tried to identify the driving forces behind the changes and understand the decisions made. Our primary sources have been people in the organization; personnel with different roles, at different levels and with different backgrounds. Our secondary sources have mainly consisted of official documents that the organization used during the implementation.We have analysed the collected data against several different organizational theories and concluded that the long sequential implementation had different focuses in different sequences. The challenge for the Armed Forces has been to create a balance between the organizations structural and the individual's human needs, and to communicate reasons and incentives for organizational change. People with power in the organization have continuously influenced the process, and the system design has self-mutated from the initial configuration to the description that exists today.The Armed Forces' structural finalization of the multi-command system has caused sub-optimization of the implementation in its final sequence, and thwarted the opportunities for mainly the specialist officer corps to develop towards a profession of its own; the category is still treated step motherly by the organization, and there is a risk of a development towards segregation and unwanted cultures. Ultimately, this has had a negative effect on The Armed Forces operational capability.The Chief of Defence decision on final implementation was necessary to shape the structure that should have been in place many years ago. However, the needs of the organization would have been better served if also the needs of the individual had been met.The Armed Forces today have a single system including all commanders on all levels, but the work is not complete. There are still some problem areas to tackle, but there are also excellent opportunities to continue the development of the system to reach an even greater effect than it has today

Försvarsmaktens befälssystem – en struktur i ständig förändring : Försvarsmaktens implementering av ett flerbefälssystem

Försvarsmaktens organisation har ett behov av ständig förändring för att kunna hantera de yttre och inre påverkansfaktorer som följer av det säkerhetspolitiska läget, samhällsutvecklingen och den teknologiska utvecklingen. Vi har genom en hermeneutisk kvalitativ studie undersökt hur organisationen förändrats genom implementeringen av ett flerbefälssystem. Vi har försökt att identifiera de drivkrafter som har legat bakom förändringarna och förstå de beslut som har fattats. Våra primärkällor har utgjorts av människor i organisationen; befattningshavare med olika roller, på olika nivåer och med olika bakgrund. Våra sekundärkällor har framförallt bestått av officiella dokument och skrivelser som organisationen nyttjat under implementeringen.Vi har analyserat inhämtad data mot flera olika organisationsteorier och kommit fram till att den långa sekventiella implementeringen haft olika fokus i olika sekvenser. Utmaningen för Försvarsmakten har varit att skapa balans mellan organisationens strukturella och individens mänskliga behov samt att kommunicera argument och incitament för organisations-förändringen. Maktpersoner i organisationen har löpande påverkat processen och systemdesignen har självmuterat från initial konfiguration till den beskrivning som finns idag.Försvarsmaktens strukturella slutinförande av Trebefälssystemet har orsakat suboptimering av implementeringen i dess sista sekvens, och motverkat möjligheterna för främst specialist-officersskrået att utvecklas mot en egen profession; skrået är fortsatt styvmoderligt behandlat av organisationen, och det finns en risk för en utveckling mot segregation och oönskade kulturer. Ytterst har detta haft en negativ effekt på den operativa förmågan.Överbefälhavarens beslut om slutligt införande var ett nödvändigt beslut för att forma den struktur som borde ha intagits för många år sedan, dock hade organisationens behov bättre kunnat omhändertas om även individens behov hade tillgodosetts.Försvarsmakten har nu ett enda system där samtligt befäl är inordnade, men arbetet är inte slutfört. Det finns fortfarande en del problemområden att ta tag i, men samtidigt också gyllene chanser att fortsätta utvecklingen av systemet för att nå än större effekt än det har idag.The Swedish Armed Forces has a need for constant change in order to be able to handle the external and internal influencing factors that result from the changing security policy situation, societal development and technological development. Through a hermeneutic qualitative study, we have investigated how the organization has changed through the implementation of a multi-command system. We have tried to identify the driving forces behind the changes and understand the decisions made. Our primary sources have been people in the organization; personnel with different roles, at different levels and with different backgrounds. Our secondary sources have mainly consisted of official documents that the organization used during the implementation.We have analysed the collected data against several different organizational theories and concluded that the long sequential implementation had different focuses in different sequences. The challenge for the Armed Forces has been to create a balance between the organizations structural and the individual's human needs, and to communicate reasons and incentives for organizational change. People with power in the organization have continuously influenced the process, and the system design has self-mutated from the initial configuration to the description that exists today.The Armed Forces' structural finalization of the multi-command system has caused sub-optimization of the implementation in its final sequence, and thwarted the opportunities for mainly the specialist officer corps to develop towards a profession of its own; the category is still treated step motherly by the organization, and there is a risk of a development towards segregation and unwanted cultures. Ultimately, this has had a negative effect on The Armed Forces operational capability.The Chief of Defence decision on final implementation was necessary to shape the structure that should have been in place many years ago. However, the needs of the organization would have been better served if also the needs of the individual had been met.The Armed Forces today have a single system including all commanders on all levels, but the work is not complete. There are still some problem areas to tackle, but there are also excellent opportunities to continue the development of the system to reach an even greater effect than it has today