Dual-trap optical tweezers with real-time force clamp control

Single molecule force clamp experiments are widely used to investigate how enzymes, molecular motors, and other molecular mechanisms work. We developed a dual-trap optical tweezers instrument with real-time (200 kHz update rate) force clamp control that can exert 0–100 pN forces on trapped beads. A model for force clamp experiments in the dumbbell-geometry is presented. We observe good agreement between predicted and observed power spectra of bead position and force fluctuations. The model can be used to predict and optimize the dynamics of real-time force clamp optical tweezers instruments. The results from a proof-of-principle experiment in which lambda exonuclease converts a double-stranded DNA tether, held at constant tension, into its single-stranded form, show that the developed instrument is suitable for experiments in single molecule biology.

Questions to Artificial Nature: A Philosophical Study of Interdisciplinary Models and their Functions in Scientific Practice

This thesis presents an interdisciplinary analysis of how models and simulations function in the production of scientific knowledge. The work is informed by three scholarly traditions: studies on models and simulations in philosophy of science, so-called micro-sociological laboratory studies within science and technology studies, and cultural-historical activity theory. Methodologically, I adopt a naturalist epistemology and combine philosophical analysis with a qualitative, empirical case study of infectious-disease modelling. This study has a dual perspective throughout the analysis: it specifies the modelling practices and examines the models as objects of research. The research questions addressed in this study are: 1) How are models constructed and what functions do they have in the production of scientific knowledge? 2) What is interdisciplinarity in model construction? 3) How do models become a general research tool and why is this process problematic? The core argument is that the mediating models as investigative instruments (cf. Morgan and Morrison 1999) take questions as a starting point, and hence their construction is intentionally guided. This argument applies the interrogative model of inquiry (e.g., Sintonen 2005; Hintikka 1981), which conceives of all knowledge acquisition as process of seeking answers to questions. The first question addresses simulation models as Artificial Nature, which is manipulated in order to answer questions that initiated the model building. This account develops further the "epistemology of simulation" (cf. Winsberg 2003) by showing the interrelatedness of researchers and their objects in the process of modelling. The second question clarifies why interdisciplinary research collaboration is demanding and difficult to maintain. The nature of the impediments to disciplinary interaction are examined by introducing the idea of object-oriented interdisciplinarity, which provides an analytical framework to study the changes in the degree of interdisciplinarity, the tools and research practices developed to support the collaboration, and the mode of collaboration in relation to the historically mutable object of research. As my interest is in the models as interdisciplinary objects, the third research problem seeks to answer my question of how we might characterise these objects, what is typical for them, and what kind of changes happen in the process of modelling. Here I examine the tension between specified, question-oriented models and more general models, and suggest that the specified models form a group of their own. I call these Tailor-made models, in opposition to the process of building a simulation platform that aims at generalisability and utility for health-policy. This tension also underlines the challenge of applying research results (or methods and tools) to discuss and solve problems in decision-making processes.

High-quality polar UV measurements : scientific analyses and transfer of the irradiance scale

The Earth's ecosystems are protected from the dangerous part of the solar ultraviolet (UV) radiation by stratospheric ozone, which absorbs most of the harmful UV wavelengths. Severe depletion of stratospheric ozone has been observed in the Antarctic region, and to a lesser extent in the Arctic and midlatitudes. Concern about the effects of increasing UV radiation on human beings and the natural environment has led to ground based monitoring of UV radiation. In order to achieve high-quality UV time series for scientific analyses, proper quality control (QC) and quality assurance (QA) procedures have to be followed. In this work, practices of QC and QA are developed for Brewer spectroradiometers and NILU-UV multifilter radiometers, which measure in the Arctic and Antarctic regions, respectively. These practices are applicable to other UV instruments as well. The spectral features and the effect of different factors affecting UV radiation were studied for the spectral UV time series at Sodankylä. The QA of the Finnish Meteorological Institute's (FMI) two Brewer spectroradiometers included daily maintenance, laboratory characterizations, the calculation of long-term spectral responsivity, data processing and quality assessment. New methods for the cosine correction, the temperature correction and the calculation of long-term changes of spectral responsivity were developed. Reconstructed UV irradiances were used as a QA tool for spectroradiometer data. The actual cosine correction factor was found to vary between 1.08-1.12 and 1.08-1.13. The temperature characterization showed a linear temperature dependence between the instrument's internal temperature and the photon counts per cycle. Both Brewers have participated in international spectroradiometer comparisons and have shown good stability. The differences between the Brewers and the portable reference spectroradiometer QASUME have been within 5% during 2002-2010. The features of the spectral UV radiation time series at Sodankylä were analysed for the time period 1990-2001. No statistically significant long-term changes in UV irradiances were found, and the results were strongly dependent on the time period studied. Ozone was the dominant factor affecting UV radiation during the springtime, whereas clouds played a more important role during the summertime. During this work, the Antarctic NILU-UV multifilter radiometer network was established by the Instituto Nacional de Meteorogía (INM) as a joint Spanish-Argentinian-Finnish cooperation project. As part of this work, the QC/QA practices of the network were developed. They included training of the operators, daily maintenance, regular lamp tests and solar comparisons with the travelling reference instrument. Drifts of up to 35% in the sensitivity of the channels of the NILU-UV multifilter radiometers were found during the first four years of operation. This work emphasized the importance of proper QC/QA, including regular lamp tests, for the multifilter radiometers also. The effect of the drifts were corrected by a method scaling the site NILU-UV channels to those of the travelling reference NILU-UV. After correction, the mean ratios of erythemally-weighted UV dose rates measured during solar comparisons between the reference NILU-UV and the site NILU-UVs were 1.007±0.011 and 1.012±0.012 for Ushuaia and Marambio, respectively, when the solar zenith angle varied up to 80°. Solar comparisons between the NILU-UVs and spectroradiometers showed a ±5% difference near local noon time, which can be seen as proof of successful QC/QA procedures and transfer of irradiance scales. This work also showed that UV measurements made in the Arctic and Antarctic can be comparable with each other.

The scientific basis and development of a matrix metalloproteinase (MMP) -8 specific chair-side test for monitoring of periodontal health and disease from gingival crevicular fluid

Matrix metalloproteinase (MMP) -8, collagenase-2, is a key mediator of irreversible tissue destruction in chronic periodontitis and detectable in gingival crevicular fluid (GCF). MMP-8 mostly originates from neutrophil leukocytes, the first line of defence cells which exist abundantly in GCF, especially in inflammation. MMP-8 is capable of degrading almost all extra-cellular matrix and basement membrane components and is especially efficient against type I collagen. Thus the expression of MMP-8 in GCF could be valuable in monitoring the activity of periodontitis and possibly offers a diagnostic means to predict progression of periodontitis. In this study the value of MMP-8 detection from GCF in monitoring of periodontal health and disease was evaluated with special reference to its ability to differentiate periodontal health and different disease states of the periodontium and to recognise the progression of periodontitis, i.e. active sites. For chair-side detection of MMP-8 from the GCF or peri-implant sulcus fluid (PISF) samples, a dip-stick test based on immunochromatography involving two monoclonal antibodies was developed. The immunoassay for the detection of MMP-8 from GCF was found to be more suitable for monitoring of periodontitis than detection of GCF elastase concentration or activity. Periodontally healthy subjects and individuals suffering of gingivitis or of periodontitis could be differentiated by means of GCF MMP-8 levels and dipstick testing when the positive threshold value of the MMP-8 chair-side test was set at 1000 µg/l. MMP-8 dipstick test results from periodontally healthy and from subjects with gingivitis were mainly negative while periodontitis patients sites with deep pockets ( 5 mm) and which were bleeding on probing were most often test positive. Periodontitis patients GCF MMP-8 levels decreased with hygiene phase periodontal treatment (scaling and root planing, SRP) and even reduced during the three month maintenance phase. A decrease in GCF MMP-8 levels could be monitored with the MMP-8 test. Agreement between the test stick and the quantitative assay was very good (κ = 0.81) and the test provided a baseline sensitivity of 0.83 and specificity of 0.96. During the 12-month longitudinal maintenance phase, periodontitis patients progressing sites (sites with an increase in attachment loss ≥ 2 mm during the maintenance phase) had elevated GCF MMP-8 levels compared with stable sites. General mean MMP-8 concentrations in smokers (S) sites were lower than in non-smokers (NS) sites but in progressing S and NS sites concentrations were at an equal level. Sites with exceptionally and repeatedly elevated MMP-8 concentrations during the maintenance phase were clustered in smoking patients with poor response to SRP (refractory patients). These sites especially were identified by the MMP-8 test. Subgingival plaque samples from periodontitis patients deep periodontal pockets were examined by polymerase chain reaction (PCR) to find out if periodontal lesions may serve as a niche for Chlamydia pneumoniae. Findings were compared with the clinical periodontal parameters and GCF MMP-8 levels to determine the correlation with periodontal status. Traces of C. pneumoniae were identified from one periodontitis patient s pooled subgingival plaque sample by means of PCR. After periodontal treatment (SRP) the sample was negative for C. pneumoniae. Clinical parameters or biomarkers (MMP-8) of the patient with the positive C. pneumoniae finding did not differ from other study patients. In this study it was concluded that MMP-8 concentrations in GCF of sites from periodontally healthy individuals, subjects with gingivitis or with periodontitis are at different levels. The cut-off value of the developed MMP-8 test is at an optimal level to differentiate between these conditions and can possibly be utilised in identification of individuals at the risk of the transition of gingivitis to periodontitis. In periodontitis patients, repeatedly elevated GCF MMP-8 concentrations may indicate sites at risk of progression of periodontitis as well as patients with poor response to conventional periodontal treatment (SRP). This can be monitored by MMP-8 testing. Despite the lower mean GCF MMP-8 concentrations in smokers, a fraction of smokers sites expressed very high MMP-8 concentrations together with enhanced periodontal activity and could be identified with MMP-8 specific chair-side test. Deep periodontal lesions may be niches for non-periodontopathogenic micro-organisms with systemic effects like C. pneumoniae and possibly play a role in the transmission from one subject to another.

Debunking Weak Sustainable Consumption : Towards Strong Sustainable Consumption Governance

Achieving sustainable consumption patterns is a crucial step on the way towards sustainability. The scientific knowledge used to decide which priorities to set and how to enforce them has to converge with societal, political, and economic initiatives on various levels: from individual household decision-making to agreements and commitments in global policy processes. The aim of this thesis is to draw a comprehensive and systematic picture of sustainable consumption and to do this it develops the concept of Strong Sustainable Consumption Governance. In this concept, consumption is understood as resource consumption. This includes consumption by industries, public consumption, and household consumption. Next to the availability of resources (including the available sink capacity of the ecosystem) and their use and distribution among the Earth’s population, the thesis also considers their contribution to human well-being. This implies giving specific attention to the levels and patterns of consumption. Methods: The thesis introduces the terminology and various concepts of Sustainable Consumption and of Governance. It briefly elaborates on the methodology of Critical Realism and its potential for analysing Sustainable Consumption. It describes the various methods on which the research is based and sets out the political implications a governance approach towards Strong Sustainable Consumption may have. Two models are developed: one for the assessment of the environmental relevance of consumption activities, another to identify the influences of globalisation on the determinants of consumption opportunities. Results: One of the major challenges for Strong Sustainable Consumption is that it is not in line with the current political mainstream: that is, the belief that economic growth can cure all our problems. So, the proponents have to battle against a strong headwind. Their motivation however is the conviction that there is no alternative. Efforts have to be taken on multiple levels by multiple actors. And all of them are needed as they constitute the individual strings that together make up the rope. However, everyone must ensure that they are pulling in the same direction. It might be useful to apply a carrot and stick strategy to stimulate public debate. The stick in this case is to create a sense of urgency. The carrot would be to articulate better the message to the public that a shrinking of the economy is not as much of a disaster as mainstream economics tends to suggest. In parallel to this it is necessary to demand that governments take responsibility for governance. The dominant strategy is still information provision. But there is ample evidence that hard policies like regulatory instruments and economic instruments are most effective. As for Civil Society Organizations it is recommended that they overcome the habit of promoting Sustainable (in fact green) Consumption by using marketing strategies and instead foster public debate in values and well-being. This includes appreciating the potential of social innovation. A countless number of such initiatives are on the way but their potential is still insufficiently explored. Beyond the question of how to multiply such approaches, it is also necessary to establish political macro structures to foster them.

Hybrid Modelling of Titan's Interaction with the Magnetosphere of Saturn

In this dissertation we study the interaction between Saturn's moon Titan and the magnetospheric plasma and magnetic field. The method of research is a three-dimensional computer simulation model, that is used to simulate this interaction. The simulation model used is a hybrid model. Hybrid models enable individual tracking or tracing of ions and also take into account the particle motion in the propagation of the electromagnetic fields. The hybrid model has been developed at the Finnish Meteorological Institute. This thesis gives a general description of the effects that the solar wind has on Earth and other planets of our solar system. Planetary satellites can also have similar interactions with the solar wind but also with the plasma flows of planetary magnetospheres. Titan is clearly the largest among the satellites of Saturn and also the only known satellite with a dense atmosphere. It is the atmosphere that makes Titan's plasma interaction with the magnetosphere of Saturn so unique. Nevertheless, comparisons with the plasma interactions of other solar system bodies are valuable. Detecting charged plasma particles requires in situ measurements obtainable through scientific spacecraft. The Cassini mission has been one of the most remarkable international efforts in space science. Since 2004 the measurements and images obtained from instruments onboard the Cassini spacecraft have increased the scientific knowledge of Saturn as well as its satellites and magnetosphere in a way no one was probably able to predict. The current level of science on Titan is practically unthinkable without the Cassini mission. Many of the observations by Cassini instrument teams have influenced this research both the direct measurements of Titan as well as observations of its plasma environment. The theoretical principles of the hybrid modelling approach are presented in connection to the broader context of plasma simulations. The developed hybrid model is described in detail: e.g. the way the equations of the hybrid model are solved is shown explicitly. Several simulation techniques, such as the grid structure and various boundary conditions, are discussed in detail as well. The testing and monitoring of simulation runs is presented as an essential routine when running sophisticated and complex models. Several significant improvements of the model, that are in preparation, are also discussed. A main part of this dissertation are four scientific articles based on the results of the Titan model. The Titan model developed during the course of the Ph.D. research has been shown to be an important tool to understand Titan's plasma interaction. One reason for this is that the structures of the magnetic field around Titan are very much three-dimensional. The simulation results give a general picture of the magnetic fields in the vicinity of Titan. The magnetic fine structure of Titan's wake as seen in the simulations seems connected to Alfvén waves an important wave mode in space plasmas. The particle escape from Titan is also a major part of these studies. Our simulations show a bending or turning of Titan's ionotail that we have shown to be a direct result of the basic principles in plasma physics. Furthermore, the ion flux from the magnetosphere of Saturn into Titan's upper atmosphere has been studied. The modelled ion flux has asymmetries that would likely have a large impact in the heating in different parts of Titan's upper atmosphere.

G.W. Leibniz and Scientific Societies

The famous philosopher Leibniz (1646-1716) was also active in the (cultural) politics of his time. His interest in forming scientific societies never waned and his efforts led to the founding of the Berlin Academy of Sciences. He also played a part in the founding of the Dresden Academy of Science and the St. Petersburg Academy of Science. Though Leibniz's models for the scientific society were the Royal Society and the Royal Science Academy of France, his pansophistic vision of scientific cooperation sometimes took on utopian dimensions. In this paper, I will present Leibniz's ideas of scientific cooperation as a kind of religious activity and discuss his various schemes for the founding of such scientific societies.

The Open Access Scientific Journal: An Empirical Study

The open access (OA) model for journals is compared to the open source principle for computer software. Since the early 1990s nearly 1,000 OA scientific journals have emerged – mostly as voluntary community efforts, although recently some professionally operating publishers have used author charges or institutional membership. This study of OA journals without author charges shows that their impact is still relatively small, but awareness of it is increasing. The average number of research articles per year is lower than for major scientific journals but the publication times are shorter.

Open Access to the Scientific Journal Literature: Situation 2009

Background: The Internet has recently made possible the free global availability of scientific journal articles. Open Access (OA) can occur either via OA scientific journals, or via authors posting manuscripts of articles published in subscription journals in open web repositories. So far there have been few systematic studies showing how big the extent of OA is, in particular studies covering all fields of science. Methodology/Principal Findings: The proportion of peer reviewed scholarly journal articles, which are available openly in full text on the web, was studied using a random sample of 1837 titles and a web search engine. Of articles published in 2008, 8,5% were freely available at the publishers’ sites. For an additional 11,9% free manuscript versions could be found using search engines, making the overall OA percentage 20,4%. Chemistry (13%) had the lowest overall share of OA, Earth Sciences (33%) the highest. In medicine, biochemistry and chemistry publishing in OA journals was more common. In all other fields author-posted manuscript copies dominated the picture. Conclusions/Significance: The results show that OA already has a significant positive impact on the availability of the scientific journal literature and that there are big differences between scientific disciplines in the uptake. Due to the lack of awareness of OA-publishing among scientists in most fields outside physics, the results should be of general interest to all scholars. The results should also interest academic publishers, who need to take into account OA in their business strategies and copyright policies, as well as research funders, who like the NIH are starting to require OA availability of results from research projects they fund. The method and search tools developed also offer a good basis for more in-depth studies as well as longitudinal studies.

Open Access to Scientific Publications – An Analysis of the Barriers to Change?

One of the effects of the Internet is that the dissemination of scientific publications in a few years has migrated to electronic formats. The basic business practices between libraries and publishers for selling and buying the content, however, have not changed much. In protest against the high subscription prices of mainstream publishers, scientists have started Open Access (OA) journals and e-print repositories, which distribute scientific information freely. Despite widespread agreement among academics that OA would be the optimal distribution mode for publicly financed research results, such channels still constitute only a marginal phenomenon in the global scholarly communication system. This paper discusses, in view of the experiences of the last ten years, the many barriers hindering a rapid proliferation of Open Access. The discussion is structured according to the main OA channels; peer-reviewed journals for primary publishing, subject- specific and institutional repositories for secondary parallel publishing. It also discusses the types of barriers, which can be classified as consisting of the legal framework, the information technology infrastructure, business models, indexing services and standards, the academic reward system, marketing, and critical mass.

Benchmarking Scientific Journals from the Submitting Author’s Viewpoint

Authors of scholarly papers to a large extent base the decision on where to submit their manuscripts on the prestige of journals, taking little account of other possible factors. Information concerning such factors is in fact often not available. This paper argues for the establishment of methods for benchmarking scientific journals, taking into account a wider range of journal performance parameters than is currently available. A model for how prospective authors determine the value of submitting to a particular journal is presented. The model includes eight factors that influence an author’s decision and 21 other underlying factors. The model is a qualitative one. The method proposes to benchmark groups of journals by application of the factors. Initial testing of the method has been undertaken in one discipline.

Scientific Journal Publishing – Yearly Volume and Open Access Availability

Introduction. We estimate the total yearly volume of peer-reviewed scientific journal articles published world-wide as well as the share of these articles available openly on the Web either directly or as copies in e-print repositories. Method. We rely on data from two commercial databases (ISI and Ulrich's Periodicals Directory) supplemented by sampling and Google searches. Analysis. A central issue is the finding that ISI-indexed journals publish far more articles per year (111) than non ISI-indexed journals (26), which means that the total figure we obtain is much lower than many earlier estimates. Our method of analysing the number of repository copies (green open access) differs from several earlier studies which have studied the number of copies in identified repositories, since we start from a random sample of articles and then test if copies can be found by a Web search engine. Results. We estimate that in 2006 the total number of articles published was approximately 1,350,000. Of this number 4.6% became immediately openly available and an additional 3.5% after an embargo period of, typically, one year. Furthermore, usable copies of 11.3% could be found in subject-specific or institutional repositories or on the home pages of the authors. Conclusions. We believe our results are the most reliable so far published and, therefore, should be useful in the on-going debate about Open Access among both academics and science policy makers. The method is replicable and also lends itself to longitudinal studies in the future.

How do Researchers Find and Retrieve Scientific Publications – A Case study of the Impact of the Internet on the Construction IT and Construction Management Research Communities

The World Wide Web provides the opportunity for a radically changed and much more efficient communication process for scientific results. A survey in the closely related domains of construction information technology and construction management was conducted in February 2000, aimed at measuring to what extent these opportunities are already changing the scientific information exchange and how researchers feel about the changes. The paper presents the results based on 236 replies to an extensive Web based questionnaire. 65% of the respondents stated their primary research interest as IT in A/E/C and 20% as construction management and economics. The questions dealt with how researchers find, access and read different sources; how much and what publications they read; how often and to which conferences they travel; how much they publish, and what are the criteria for where they eventually decide to publish. Some of the questions confronted traditional and electronic publishing with one final section dedicated to opinions about electronic publishing. According to the survey researchers already download half of the material that they read digitally from the Web. The most popular method for retrieving an interesting publication is downloading it for free from the author’s or publisher’s website. Researchers are not particularly willing to pay for electronic scientific publications. There is much support for a scenario of electronic journals available totally freely on the Web, where the costs could be covered by for instance professional societies or the publishing university. The shift that the Web is causing seems to be towards the "just in time" reading of literature. Also, frequent users of the Web rely less on scientific publications and tend to read fewer articles. If available with little effort, papers published in traditional journals are preferred; if not, the papers should be on the Web. In these circumstances, the role of paper-based journals published by established publishers is shifting from the core "information exchange" to the building of authors' prestige. The respondents feel they should build up their reputations by publishing in journals and relevant conferences, but then make their work freely available on the Web.