Exit times for some processes with normally distributed noise

Denna avhandling handlar om metoder för att hitta begränsningar för det asymptotiska beteendet hos en förväntad uthoppstid från ett område omkring en xpunkt för processer som har normalfördelad störning. I huvudsak behandlas olika typer av autoregressiva processer. Fyra olika metoder används. En metod som använder principen för stora avvikelser samt en metod som jämför uthoppstiden med en återkomsttid ger övre begränsningar för den förväntade uthoppstiden. En martingalmetod och en metod för normalfördelade stokastiska variabler ger undre begränsningar. Metoderna har alla både förtjänster och nackdelar. Genom att kombinera de olika metoderna får man de bästa resultaten. Vi får fram gränsvärdet för det asymptotiska beteendet hos en uthoppstid för den multivariata autoregressiva processen, samt motsvarande gränsvärde för den univariata autoregressiva processen av ordning n.

Using green fluorescent protein to understand the mechanisms of G-protein-coupled receptor regulation

G protein-coupled receptor (GPCR) activation is followed rapidly by adaptive changes that serve to diminish the responsiveness of a cell to further stimulation. This process, termed desensitization, is the consequence of receptor phosphorylation, arrestin binding, sequestration and down-regulation. GPCR phosphorylation is initiated within seconds to minutes of receptor activation and is mediated by both second messenger-dependent protein kinases and receptor-specific G protein-coupled receptor kinases (GRKs). Desensitization in response to GRK-mediated phosphorylation involves the binding of arrestin proteins that serve to sterically uncouple the receptor from its G protein. GPCR sequestration, the endocytosis of receptors to endosomes, not only contributes to the temporal desensitization of GPCRs, but plays a critical role in GPCR resensitization. GPCR down-regulation, a loss of the total cellular complement of receptors, is the consequence of both increased lysosomal degradation and decreased mRNA synthesis of GPCRs. While each of these agonist-mediated desensitization processes are initiated within a temporally dissociable time frame, recent data suggest that they are intimately related to one another. The use of green fluorescent protein from the jellyfish Aqueora victoria as an epitope tag with intrinsic fluorescence has facilitated our understanding of the relative relationship between GRK phosphorylation, arrestin binding, receptor sequestration and down-regulation.

Fluorescent ligands for studying neuropeptide receptors by confocal microscopy

This paper reviews the use of confocal microscopy as it pertains to the identification of G-protein coupled receptors and the study of their dynamic properties in cell cultures and in mammalian brain following their tagging with specific fluorescent ligands. Principles that should guide the choice of suitable ligands and fluorophores are discussed. Examples are provided from the work carried out in the authors' laboratory using custom synthetized fluoresceinylated or BODIPY-tagged bioactive peptides. The results show that confocal microscopic detection of specifically bound fluorescent ligands permits high resolution appraisal of neuropeptide receptor distribution both in cell culture and in brain sections. Within the framework of time course experiments, it also allows for a dynamic assessment of the internalization and subsequent intracellular trafficking of bound fluorescent molecules. Thus, it was found that neurotensin, somatostatin and mu- and delta-selective opioid peptides are internalized in a receptor-dependent fashion and according to receptor-specific patterns into their target cells. In the case of neurotensin, this internalization process was found to be clathrin-mediated, to proceed through classical endosomal pathways and, in neurons, to result in a mobilization of newly formed endosomes from neural processes to nerve cell bodies and from the periphery of cell bodies towards the perinuclear zone. These mechanisms are likely to play an important role for ligand inactivation, receptor regulation and perhaps also transmembrane signaling.

Immunization by subcutaneous implants of polyester-polyurethane sponges coupled with antigen

A new protocol is described for immunization of outbred Swiss mice. The procedure is based on subcutaneous implantation of antigen-coupled polyester-polyurethane sponges cut into disks of 10 mm in diameter vs 2 mm in thickness. Antigen coupling was performed by overnight incubation of the sponge with a solution of ovalbumin (Ova) (2 mg/ml) diluted in sodium carbonate buffer, pH 9.6. The amount of ovalbumin that was taken up by the sponge was between 71.4 to 82.5 µg. This was estimated by comparing the Ova absorbance at 280 nm in coating buffer solutions before and after incubation. To compare the efficiency of the proposed method, experimental groups immunized with the antigen in the presence of adjuvants (10 µg in Al(OH)3 or 100 µg in complete Freund's adjuvant (CFA)) were run in parallel. The data obtained after the 3rd week of immunization indicate that both cellular and humoral immune responses were achieved. These were assayed by antigen-induced footpad swelling and ELISA (specific antibodies), respectively. The levels of both immune responses elicited were similar to the responses observed in mice immunized with ovalbumin in the presence of Al(OH)3. The method might represent an advantage when immunizing with pathogenic antigens. Preliminary experiments have suggested that the antigen remains immobilized or bound to the sponge for a long period of time, since there is an increment on the cell population inside the sponges after boosting the animals. If so, the undesirable effects of immunization would be reduced.

An optically coupled power stimulus isolation unit with high voltage and fast rise time output

Recent technological developments have created new devices that could improve and simplify the construction of stimulus isolators. HEXFET transistors can switch large currents and hundreds of volts in nanoseconds. The newer opto-isolators can give a pulse rise time of a few nanoseconds, with output compatible with MOSFET devices, in which delays are reduced to nanoseconds. Integrated DC/DC converters are now available. Using these new resources we developed a new electrical stimulus isolator circuit with selectable constant-current and constant-voltage modes, which are precise and easy to construct. The circuit works like a regulated power supply in both modes with output switched to zero or to free mode through an opto-isolator device. The isolator analyses showed good practical performance. The output to ground resistance was 1011 ohms and capacitance 35 picofarads. The rise time and fall time were identical (5 µs) and constant. The selectable voltage or current output mode made it very convenient to use. The current mode, with higher output resistance values in low current ranges, permits intracellular stimulation even with tip resistances close to 100 megaohms. The high compliance of 200 V guarantees the value of the current stimulus. The very low output resistance in the voltage mode made the device highly suitable for extracellular stimulation with low impedance electrodes. Most importantly, these characteristics were achieved with a circuit that was easy to build and modify and assembled with components available in Brazil.

Designing sustainable industrial ecosystems : the case of a biogas-for-traffic solution

This thesis focuses on the development of sustainable industrial architectures for bioenergy based on the metaphors of industrial symbiosis and industrial ecosystems, which imply exchange of material and energy side-flows of various industries in order to improve sustainability of those industries on a system level. The studies on industrial symbiosis have been criticised for staying at the level of incremental changes by striving for cycling waste and by-flows of the industries ‘as is’ and leaving the underlying industry structures intact. Moreover, there has been articulated the need for interdisciplinary research on industrial ecosystems as well as the need to extend the management and business perspectives on industrial ecology. This thesis addresses this call by applying a business ecosystem and business model perspective on industrial symbiosis in order to produce knowledge on how industrial ecosystems can be developed that are sustainable environmentally and economically. A case of biogas business is explored and described in four research papers and an extended summary that form this thesis. Since the aim of the research was to produce a normative model for developing sustainable industrial ecosystems, the methodology applied in this research can be characterised as constructive and collaborative. A constructive research mode was required in order to expand the historical knowledge on industrial symbiosis development and business ecosystem development into the knowledge of what should be done, which is crucial for sustainability and the social change it requires. A collaborative research mode was employed through participating in a series of projects devoted to the development of a biogas-for-traffic industrial ecosystem. The results of the study showed that the development of material flow interconnections within industrial symbiosis is inseparable from larger business ecosystem restructuring. This included a shift in the logic of the biogas and traffic fuel industry and a subsequent development of a business ecosystem that would entail the principles of industrial symbiosis and localised energy production and consumption. Since a company perspective has been taken in this thesis, the role of an ecosystem integrator appeared as a crucial means to achieve the required industry restructuring. This, in turn, required the development of a modular and boundary-spanning business model that had a strong focus on establishing collaboration among ecosystem stakeholders and development of multiple local industrial ecosystems as part of business growth. As a result, the designed business model of the ecosystem integrator acquired the necessary flexibility in order to adjust to local conditions, which is crucial for establishing industrial symbiosis. This thesis presents a normative model for the development of a business model required for creating sustainable industrial ecosystems, which contributes to approaches at the policy-makers’ level, proposed earlier. Therefore, this study addresses the call for more research on the business level of industrial ecosystem formation and the implications for the business models of the involved actors. Moreover, the thesis increases the understanding of system innovation and innovation in business ecosystems by explicating how business model innovation can be the trigger for achieving more sustainable industry structures, such as those relying on industrial symbiosis.

The use of filter paper plasticized with polyvinyl alcohol-glutaraldehyde in ELISA

F1-antigen purified from Yersinia pestis was covalently linked to 5-mm diameter filter paper discs plasticized with polyvinyl alcohol-glutaraldehyde. These discs were used both for ELISA and dot-ELISA for the detection of anti-F1 IgG in rabbits. The best conditions were achieved using 1.25 µg of F1 antigen/disc, 3% w/v skim milk in PBS as blocking agent, anti-IgG peroxidase conjugate diluted 12,000 times, and serum from rabbits immunized or not against Y. pestis, diluted 6,400 times. The absorbance values obtained from the comparative study between this procedure and conventional ELISA were not significantly different but the low cost of the reagents employed in ELISA using the filter paper discs plasticized with polyvinyl alcohol-glutaraldehyde makes this method economically attractive.

Narrow-band 1, 2, 3, 4, 8, 16 and 24 cycles/360º angular frequency filters

We measured human frequency response functions for seven angular frequency filters whose test frequencies were centered at 1, 2, 3, 4, 8, 16 or 24 cycles/360º using a supra-threshold summation method. The seven functions of 17 experimental conditions each were measured nine times for five observers. For the arbitrarily selected filter phases, the maximum summation effect occurred at test frequency for filters at 1, 2, 3, 4 and 8 cycles/360º. For both 16 and 24 cycles/360º test frequencies, maximum summation occurred at the lower harmonics. These results allow us to conclude that there are narrow-band angular frequency filters operating somehow in the human visual system either through summation or inhibition of specific frequency ranges. Furthermore, as a general result, it appears that addition of higher angular frequencies to lower ones disturbs low angular frequency perception (i.e., 1, 2, 3 and 4 cycles/360º), whereas addition of lower harmonics to higher ones seems to improve detection of high angular frequency harmonics (i.e., 8, 16 and 24 cycles/360º). Finally, we discuss the possible involvement of coupled radial and angular frequency filters in face perception using an example where narrow-band low angular frequency filters could have a major role.

On Distributed Storage Codes

Distributed storage systems are studied. The interest in such system has become relatively wide due to the increasing amount of information needed to be stored in data centers or different kinds of cloud systems. There are many kinds of solutions for storing the information into distributed devices regarding the needs of the system designer. This thesis studies the questions of designing such storage systems and also fundamental limits of such systems. Namely, the subjects of interest of this thesis include heterogeneous distributed storage systems, distributed storage systems with the exact repair property, and locally repairable codes. For distributed storage systems with either functional or exact repair, capacity results are proved. In the case of locally repairable codes, the minimum distance is studied. Constructions for exact-repairing codes between minimum bandwidth regeneration (MBR) and minimum storage regeneration (MSR) points are given. These codes exceed the time-sharing line of the extremal points in many cases. Other properties of exact-regenerating codes are also studied. For the heterogeneous setup, the main result is that the capacity of such systems is always smaller than or equal to the capacity of a homogeneous system with symmetric repair with average node size and average repair bandwidth. A randomized construction for a locally repairable code with good minimum distance is given. It is shown that a random linear code of certain natural type has a good minimum distance with high probability. Other properties of locally repairable codes are also studied.

Disintegrins: integrin selective ligands which activate integrin-coupled signaling and modulate leukocyte functions

Extracellular matrix proteins and cell adhesion receptors (integrins) play essential roles in the regulation of cell adhesion and migration. Interactions of integrins with the extracellular matrix proteins lead to phosphorylation of several intracellular proteins such as focal adhesion kinase, activating different signaling pathways responsible for the regulation of a variety of cell functions, including cytoskeleton mobilization. Once leukocytes are guided to sites of infection, inflammation, or antigen presentation, integrins can participate in the initiation, maintenance, or termination of the immune and inflammatory responses. The modulation of neutrophil activation through integrin-mediated pathways is important in the homeostatic control of the resolution of inflammatory states. In addition, during recirculation, T lymphocyte movement through distinct microenvironments is mediated by integrins, which are critical for cell cycle, differentiation and gene expression. Disintegrins are a family of low-molecular weight, cysteine-rich peptides first identified in snake venom, usually containing an RGD (Arg-Gly-Asp) motif, which confers the ability to selectively bind to integrins, inhibiting integrin-related functions in different cell systems. In this review we show that, depending on the cell type and the microenvironment, disintegrins are able to antagonize the effects of integrins or to act agonistically by activating integrin-mediated signaling. Disintegrins have proven useful as tools to improve the understanding of the molecular events regulated by integrin signaling in leukocytes and prototypes in order to design therapies able to interfere with integrin-mediated effects.

Kalman filter for computational market dynamics

Kalman filter is a recursive mathematical power tool that plays an increasingly vital role in innumerable fields of study. The filter has been put to service in a multitude of studies involving both time series modelling and financial time series modelling. Modelling time series data in Computational Market Dynamics (CMD) can be accomplished using the Jablonska-Capasso-Morale (JCM) model. Maximum likelihood approach has always been utilised to estimate the parameters of the JCM model. The purpose of this study is to discover if the Kalman filter can be effectively utilized in CMD. Ensemble Kalman filter (EnKF), with 50 ensemble members, applied to US sugar prices spanning the period of January, 1960 to February, 2012 was employed for this work. The real data and Kalman filter trajectories showed no significant discrepancies, hence indicating satisfactory performance of the technique. Since only US sugar prices were utilized, it would be interesting to discover the nature of results if other data sets are employed.

Initialization of Continuous Nonlinear Models Using Extended Kalman Filter

The two main objectives of Bayesian inference are to estimate parameters and states. In this thesis, we are interested in how this can be done in the framework of state-space models when there is a complete or partial lack of knowledge of the initial state of a continuous nonlinear dynamical system. In literature, similar problems have been referred to as diffuse initialization problems. This is achieved first by extending the previously developed diffuse initialization Kalman filtering techniques for discrete systems to continuous systems. The second objective is to estimate parameters using MCMC methods with a likelihood function obtained from the diffuse filtering. These methods are tried on the data collected from the 1995 Ebola outbreak in Kikwit, DRC in order to estimate the parameters of the system.

Customer involvement in lean startup principles: case of game development studio

The objective of this thesis is to better understand customer’s role in lean startup methodology. The aim is to find out how customers are involved in lean startup methodology implantation and increase the likelihood of new venture survival. This study emphasizes the usage of customers in shaping of new product development processes within companies, through iteration and constant communication. This communication facilitates the development of features that are requested by the customers and enhances the prospects of the new venture. The empirical part of the study is a single qualitative case study that uses action research to implement the lean startup methodology into a pre-revenue venture and examines its customer involvement processes. The studied case company is Karaoke d.o.o., developing a game called kParty. The study used the theory discussed in the literature review: customer involvement (in the survey and interviews conducted for the lean startup methodology), lean principles (through the implementation of lean startup methodology) and lean startup methodology, which are the central building parts of this thesis as a whole. The thesis contributes to the understanding of customer involvement in lean startup methodology, while giving practical implications of customer orientation and product market fitting.

First-principles study on electronic and structural properties of Cu(In/Ga)Se alloys for solar cells

Thin-film photovoltaic solar cells based on the Cu(In1−xGax)Se2 (CIGS) alloys have attracted more and more attention due to their large optical absorption coefficient, long term stability, low cost, and high efficiency. Modern theoretical studies of this material with first-principles calculations can provide accurate description of the electronic structure and yield results in close agreement with experimental values, but takes a large amount of calculation time. In this work, we use first-principles calculations based on the computationally affordable meta- generalized gradient approximation of the density-functional theory to investigate electronic and structural properties of the CIGS alloys. We report on the simulation of the lattice parameters and band gaps, as a function of chemical composition. The obtained results were found to be in a good agreement with the available experimental data.

Kraft recovery boilers – Principles and practice

This book was created as postgraduate lecture notes for Lappeenranta University of Technology's special course of steam power plants. But as with anything ever written the ideas shown have nurtured for a long time. Parts of these chapters have appeared elsewhere as individual papers or work documents. One of the most helpful episodes have been presentations and discussions during Pohto Operator training seminars. Input from those sessions can be seen in chapter firing. You who run recovery boilers, I salute you. The purpose of this text is to give the reader an overview of recovery boiler operation. Most parts of the recovery boiler operation are common to boilers burning other fuels. The furnace operation differs significantly from operation of other boiler furnaces. Oxygen rich atmosphere is needed to burn fuel efficiently. But the main function of recovery boiler is to reduce spent cooking chemicals. Reduction reactions happen best in oxygen deficient atmosphere. This dual, conflicting nature of recovery furnace makes understanding it so challenging. To understand the processes happening in the recovery furnace one must try to understand the detailed processes that might occur and their limitations. Therefore chapters on materials, corrosion and fouling have been added.