Adaptive Routing Approaches for Networked Many-Core Systems

Through advances in technology, System-on-Chip design is moving towards integrating tens to hundreds of intellectual property blocks into a single chip. In such a many-core system, on-chip communication becomes a performance bottleneck for high performance designs. Network-on-Chip (NoC) has emerged as a viable solution for the communication challenges in highly complex chips. The NoC architecture paradigm, based on a modular packet-switched mechanism, can address many of the on-chip communication challenges such as wiring complexity, communication latency, and bandwidth. Furthermore, the combined benefits of 3D IC and NoC schemes provide the possibility of designing a high performance system in a limited chip area. The major advantages of 3D NoCs are the considerable reductions in average latency and power consumption. There are several factors degrading the performance of NoCs. In this thesis, we investigate three main performance-limiting factors: network congestion, faults, and the lack of efficient multicast support. We address these issues by the means of routing algorithms. Congestion of data packets may lead to increased network latency and power consumption. Thus, we propose three different approaches for alleviating such congestion in the network. The first approach is based on measuring the congestion information in different regions of the network, distributing the information over the network, and utilizing this information when making a routing decision. The second approach employs a learning method to dynamically find the less congested routes according to the underlying traffic. The third approach is based on a fuzzy-logic technique to perform better routing decisions when traffic information of different routes is available. Faults affect performance significantly, as then packets should take longer paths in order to be routed around the faults, which in turn increases congestion around the faulty regions. We propose four methods to tolerate faults at the link and switch level by using only the shortest paths as long as such path exists. The unique characteristic among these methods is the toleration of faults while also maintaining the performance of NoCs. To the best of our knowledge, these algorithms are the first approaches to bypassing faults prior to reaching them while avoiding unnecessary misrouting of packets. Current implementations of multicast communication result in a significant performance loss for unicast traffic. This is due to the fact that the routing rules of multicast packets limit the adaptivity of unicast packets. We present an approach in which both unicast and multicast packets can be efficiently routed within the network. While suggesting a more efficient multicast support, the proposed approach does not affect the performance of unicast routing at all. In addition, in order to reduce the overall path length of multicast packets, we present several partitioning methods along with their analytical models for latency measurement. This approach is discussed in the context of 3D mesh networks.

Integration of learning supportive applications into the development of the e-portfolio construction process

The portfolio as a means of demonstrating personal skills has lately been gaining prominence among technology students. This is partially due to the introduction of electronic portfolios, or e-portfolios. As platforms for e-portfolio management with different approaches have been introduced, the learning cycle, traditional portfolio pedagogy, and learner centricity have sometimes been forgotten, and as a result, the tools have been used for the most part as data depositories. The purpose of this thesis is to show how the construction of e-portfolios of IT students can be supported by institutions through the usage of different tools that relate to study advising, teaching, and learning. The construction process is presented as a cycle based on learning theories. Actions related to the various phases of the e-portfolio construction process are supported by the implementation of software applications. To maximize learner-centricity and minimize the intervention of the institution, the evaluated and controlled actions for these practices can be separated from the e-portfolios, leaving the construction of the e-portfolio to students. The main contributions of this thesis are the implemented applications, which can be considered to support the e-portfolio construction by assisting in planning, organizing, and reflecting activities. Eventually, this supports the students in their construction of better and more extensive e-portfolios. The implemented tools include 1) JobSkillSearcher to help students’ recognition of the demands of the ICT industry regarding skills, 2) WebTUTOR to support students’ personal study planning, 3) Learning Styles to determine students' learning styles, and 4) MyPeerReview to provide a platform on which to carry out anonymous peer review processes in courses. The most visible outcome concerning the e-portfolio is its representation, meaning that one can use it to demonstrate personal achievements at the time of seeking a job and gaining employment. Testing the tools and the selected open-source e-portfolio application indicates that the degree of richness of e-portfolio content can be increased by using the implemented applications.

Corporate Social Responsibility and Shipping Views of Baltic Sea Shipping Companies on the Benefits of Responsibility

The safety of shipping operations in the Baltic Sea is an extensively studied issue due to the density of traffic and the ecological sensitivity of the area. The focus has, however, mainly been on ship technology or on traffic control measures and the operative safety aspect of shipping is in a minor position in maritime safety studies and is lacking in terms of solutions. Self-regulatory and voluntary measures could be effective ways to improve the operational safety of shipping. Corporate social responsibility, or CSR, is one example of a voluntary measure that the shipping companies can take. CSR can enhance maritime safety and improve the shipping companies’ competitiveness. The aim of this study is to increase the knowledge of CSR in the maritime sector and study its applicability and benefits to the shipping companies. The research comprises of a theory part and a questionnaire study, which examine the significance of corporate social responsibility in shipping companies’ maritime safety and competitiveness. The aim of the questionnaire study is to find out how corporate social responsibility is implemented in the shipping companies. According to the literature review, responsible actions can produce financial and time costs, but due to these actions cost savings in the form of learning and increased efficiency can be achieved. Responsible actions can also produce concrete improvements and a reputation of responsibility that can lead to both cost savings and increase in the company’s income. CSR is recognised as having real business benefits in terms of attracting customers and high-quality employees. In shipping, CSR usually focuses on environmental issues. Environmental social responsibility in shipping is mainly motivated by the need to comply with existing and forthcoming regulation. Shipping companies engage in CSR to gain competitive advantage and to increase maritime safety. The social aspects of CSR take into account the well-being and skills of the employees, corporation and other stakeholders of the company. The questionnaire study revealed that the most common CSR measures in shipping companies are environmental measures, and that environmental concerns are considered to be the most important reason to engage in CSR. From the preliminary question about the concept of CSR it can also be seen that safety issues are commonly considered to be a part of CSR and safety gains are the second most important reason to engage in CSR. From the questionnaire, it can also be extrapolated that gaining a better reputation is one of the most important reasons to engage in CSR in the first place. For example, the main economic benefit was seen to be the increase of customer numbers as a result of a better reputation. Based on the study, it would seem that companies are starting to realise that they might gain competitive advantage and be favoured as shippers if they engage in sustainable, responsible operations and present themselves as “green”.

Mitigation possibilities to Greenhouse gas emissions from power production in India

Global warming is assertively the greatest environmental challenge for humans of 21st century. It is primarily caused by the anthropogenic greenhouse gas (GHG) that trap heat in the atmosphere. Because of which, the GHG emission mitigation, globally, is a critical issue in the political agenda of all high-profile nations. India, like other developing countries, is facing this threat of climate change while dealing with the challenge of sustaining its rapid economic growth. India’s economy is closely connected to its natural resource base and climate sensitive sectors like water, agriculture and forestry. Due to Climate change the quality and distribution of India’s natural resources may transform and lead to adverse effects on livelihood of its people. Therefore, India is expected to face a major threat due to the projected climate change. This study proposes possible solutions for GHG emission mitigation that are specific to the power sector of India. The methods discussed here will take Indian power sector from present coal dominant ideology to a system, centered with renewable energy sources. The study further proposes a future scenario for 2050, based on the present Indian government policies and global energy technologies advancements.

The good and the successful - Examination of informal learning mechanisms

This thesis strived to find out which informal learning (IL) mechanisms are used the most by the respondents. Additionally, the goal was to know more about the respondents as informal learners and what could explain possible differences. The target was to resolve whether informal learning explains differences in individual performance or, do some other explanations for success exist. Informal learning was to be made more visible, since many are unaware of it. Relevant IL mechanisms that the interviewees could explain were selected for this thesis. The theory on informal learning was presented and some additional informal learning mechanisms were included: Underlying learning theories, internal and external learning resources, as well as some sport related informal learning mechanisms. Various scholars have explained these terms. The final results of this thesis relate to business context, but sport is at the scope of my research. The target group consisted of nine individuals in team sports that were considered as high performers (good/successful). Hence, also the concept of high performance was clarified with competence, expertise and talent literature. The study is qualitative and face-to-face interviews were chosen. The data was analyzed with Grounded Theory principles and theory elaboration. This thesis pointed out similarities and differences between the respondents´ answers (good/successful, inexperienced/experienced). Thus, the analysis clarified that there are different attitudes to learning and different learner profiles in sports context. Also, it became clear that some informal learning mechanisms are more used than others. Secondly, based on the most crucial differences, Typology of Talentum was formulated based on Le Deist & Winteron´s (2005, 39) Typology of holistic competence. Some variables of informal learning seemed to constitute the Meta-competence of Typology that ultimately causes the differences in individual performance and success. The results can be transferred to business context because meta-competence is transferable by nature.

Evaluation of an e-learning course: coercion practices in psychiatric nursing

The goal of the study was to evaluate an e-learning course entitled “Nursing interventions to manage distressed and disturbed patients” and intended for psychiatric nurses, using Kirkpatrick’s evaluation model. The aim was to describe nurses’ reactions, learning, behaviour change and impacts resulting from this e-learning course. This dissertation comprises four papers, and the data were collected 2008-2012 from three different sources; electronic databases, an e-learning platform and psychiatric hospitals. First, a systematic literature review was conducted to understand the effectiveness of e-learning. Second, an RCT study was implemented to investigate the impact of the e-learning course on nurses’ job-satisfaction, knowledge and attitudes (N=158). Third, to complete the picture of nurses views of the e-learning course related to knowledge transfer, the nurses’ perspective was studied (N=33). Lastly, the effects of the e-learning course from nursing managers’ perspective in psychiatric hospital organisations were studied (N=28). The systematic review showed that although the nurses were satisfied with the e-learning, no effects were found in the RCT study of nurses’ job satisfaction. The RCT study showed no effects on nurses’ learning related to knowledge increase, but there was change in attitudes. The managers described the changes in the nurses’ knowledge and attitudes. Among the nurses behaviour changed with knowledge transfer from the e-learning course to practice and they pointed out development issues related to their work. The final impacts of the e-learning course revealed advantages and disadvantages of the e-learning course and its implications for nurses’ work. This dissertation provides new insight into nurses’ reactions, learning, behaviour change and impacts resulting from an e-learning course in their continuing education. In order to improve nurses’ continuing education systematic evaluation is needed, for which Kirkpatrick’s evaluation model is a useful tool.

Design and evaluation of web interface signs to improve web usability : a semiotic framework

Technological innovations, the development of the internet, and globalization have increased the number and complexity of web applications. As a result, keeping web user interfaces understandable and usable (in terms of ease-of-use, effectiveness, and satisfaction) is a challenge. As part of this, designing userintuitive interface signs (i.e., the small elements of web user interface, e.g., navigational link, command buttons, icons, small images, thumbnails, etc.) is an issue for designers. Interface signs are key elements of web user interfaces because ‘interface signs’ act as a communication artefact to convey web content and system functionality, and because users interact with systems by means of interface signs. In the light of the above, applying semiotic (i.e., the study of signs) concepts on web interface signs will contribute to discover new and important perspectives on web user interface design and evaluation. The thesis mainly focuses on web interface signs and uses the theory of semiotic as a background theory. The underlying aim of this thesis is to provide valuable insights to design and evaluate web user interfaces from a semiotic perspective in order to improve overall web usability. The fundamental research question is formulated as What do practitioners and researchers need to be aware of from a semiotic perspective when designing or evaluating web user interfaces to improve web usability? From a methodological perspective, the thesis follows a design science research (DSR) approach. A systematic literature review and six empirical studies are carried out in this thesis. The empirical studies are carried out with a total of 74 participants in Finland. The steps of a design science research process are followed while the studies were designed and conducted; that includes (a) problem identification and motivation, (b) definition of objectives of a solution, (c) design and development, (d) demonstration, (e) evaluation, and (f) communication. The data is collected using observations in a usability testing lab, by analytical (expert) inspection, with questionnaires, and in structured and semi-structured interviews. User behaviour analysis, qualitative analysis and statistics are used to analyze the study data. The results are summarized as follows and have lead to the following contributions. Firstly, the results present the current status of semiotic research in UI design and evaluation and highlight the importance of considering semiotic concepts in UI design and evaluation. Secondly, the thesis explores interface sign ontologies (i.e., sets of concepts and skills that a user should know to interpret the meaning of interface signs) by providing a set of ontologies used to interpret the meaning of interface signs, and by providing a set of features related to ontology mapping in interpreting the meaning of interface signs. Thirdly, the thesis explores the value of integrating semiotic concepts in usability testing. Fourthly, the thesis proposes a semiotic framework (Semiotic Interface sign Design and Evaluation – SIDE) for interface sign design and evaluation in order to make them intuitive for end users and to improve web usability. The SIDE framework includes a set of determinants and attributes of user-intuitive interface signs, and a set of semiotic heuristics to design and evaluate interface signs. Finally, the thesis assesses (a) the quality of the SIDE framework in terms of performance metrics (e.g., thoroughness, validity, effectiveness, reliability, etc.) and (b) the contributions of the SIDE framework from the evaluators’ perspective.

Human_Leishmaniasis@cytokines.bahia.br

The cell-mediated immune response is critical in the resistance to and recovery from leishmaniasis. Cytokines are central elements in mounting an immune response and have received a great deal of attention in both human and experimental leishmaniasis. IFN-g is responsible for macrophage activation leading to leishmanicidal mechanisms. Understanding the balance of cytokines that lead to enhanced production of or synergize with IFN-g, and those cytokines that counterbalance its effects is fundamental for developing rational immunotherapeutic or immunoprophylactic approaches to leishmaniasis. Here we focus on the cytokine balance in human leishmaniasis, particularly IL-10 as an IFN-g opposing cytokine, and IL-12 as an IFN-g inducer. The effects of these cytokines were evaluated in terms of several parameters of the human immune response. IL-10 reduced lymphocyte proliferation, IFN-g production and cytotoxic activity of responsive human peripheral blood mononuclear cells. Neutralization of IL-10 led to partial restoration of lymphoproliferation, IFN-g production and cytotoxic activity in unresponsive visceral leishmaniasis patients. IL-12 also restored the responses of peripheral blood mononuclear cells from visceral leishmaniasis patients. The responses obtained with IL-12 are higher than those obtained with anti-IL-10, even when anti-IL-10 is combined with anti-IL-4

Carbon monoxide: from toxin to endogenous modulator of cardiovascular functions

Carbon monoxide (CO) is a pollutant commonly recognized for its toxicological attributes, including CNS and cardiovascular effects. But CO is also formed endogenously in mammalian tissues. Endogenously formed CO normally arises from heme degradation in a reaction catalyzed by heme oxygenase. While inhibitors of endogenous CO production can raise arterial pressure, heme loading can enhance CO production and lead to vasodepression. Both central and peripheral tissues possess heme oxygenases and generate CO from heme, but the inability of heme substrate to cross the blood brain barrier suggests the CNS heme-heme oxygenase-CO system may be independent of the periphery. In the CNS, CO apparently acts in the nucleus tractus solitarii (NTS) promoting changes in glutamatergic neurotransmission and lowering blood pressure. At the periphery, the heme-heme oxygenase-CO system can affect cardiovascular functions in a two-fold manner; specifically: 1) heme-derived CO generated within vascular smooth muscle (VSM) can promote vasodilation, but 2) its actions on the endothelium apparently can promote vasoconstriction. Thus, it seems reasonable that the CNS-, VSM- and endothelial-dependent actions of the heme-heme oxygenase-CO system may all affect cardiac output and vascular resistance, and subsequently blood pressure.

Developed pressure data may provide misinformation when used alone to evaluate systolic function in isovolumetric left ventricle preparations

We report data showing that developed pressure (DPmax) may lead to opposite conclusion with respect to maximal developed circumferential wall stress (smax) when used to assess contractile function in left ventricle isovolumic preparations. Isovolumetric left ventricle preparations of rats with cardiac hypertrophy (H; N = 10) induced by isoproterenol administration showed higher DPmax (174 ± 14 mmHg) than control (C; N = 8) animals (155 ± 12 mmHg) or rats with regression (R; N = 8) of hypertrophy (144 ± 11 mmHg). In contrast, the estimated smax for C (145 ± 26 kdynes/cm2) and R (133 ± 17 kdynes/cm2) was higher than for H (110 ± 13 kdynes/cm2). According to Laplace's law, the opposite results of DPmax and smax may depend on the increased mass/volume left ventricle ratio of the hypertrophied hearts, which favored pressure generation. These results clearly show that DPmax should be used with caution to analyze systolic function.

Control of CD4 gene expression: connecting signals to outcomes in T cell development

The control of CD4 gene expression is essential for proper T lymphocyte development. Signals transmitted from the T-cell antigen receptor (TCR) during the thymic selection processes are believed to be linked to the regulation of CD4 gene expression during specific stages of T cell development. Thus, a study of the factors that control CD4 gene expression may lead to further insight into the molecular mechanisms that drive thymic selection. In this review, we discuss the work conducted to date to identify and characterize the cis-acting transcriptional control elements in the CD4 locus and the DNA-binding factors that mediate their function. From these studies, it is becoming clear that the molecular mechanisms controlling CD4 gene expression are very complex and differ at each stage of development. Thus, the control of CD4 expression is subject to many different influences as the thymocyte develops.

Learning information technology business in a changing industry landscape. Introducing Team Entrepreneurship in Renewing Bachelor Education in Renewing Bachelor Education in Information

Speed, uncertainty and complexity are increasing in the business world all the time. When knowledge and skills become quickly irrelevant, new challenges are set for information technology (IT) education. Meta-learning skills – learning how to learn rapidly - and innovation skills have become more essential than single technologies or other specific issues. The drastic changes in the information and communications technology (ICT) sector have caused a need to reconsider how IT Bachelor education in Universities of Applied Sciences should be organized and employed to cope with the change. The objective of the study was to evaluate how a new approach to IT Bachelor education, the ICT entrepreneurship study path (ICT-ESP) fits IT Bachelor education in a Finnish University of Applied Sciences. This kind of educational arrangement has not been employed elsewhere in the context of IT Bachelor education. The study presents the results of a four-year period during which IT Bachelor education was renewed in a Finnish University of Applied Sciences. The learning environment was organized into an ICT-ESP based on Nonaka’s knowledge theory and Kolb’s experiental learning. The IT students who studied in the ICT-ESP established a cooperative and learned ICT by running their cooperative at the University of Applied Sciences. The students (called team entrepreneurs) studied by reading theory in books and other sources of explicit information, doing projects for their customers, and reflecting in training sessions on what was learnt by doing and by studying the literature. Action research was used as the research strategy in this study. Empirical data was collected via theme-based interviews, direct observation, and participative observation. Grounded theory method was utilized in the data analysis and the theoretical sampling was used to guide the data collection. The context of the University of Applied Sciences provided a good basis for fostering team entrepreneurship. However, the results showed that the employment of the ICT-ESP did not fit into the IT Bachelor education well enough. The ICT-ESP was cognitively too tough for the team entrepreneurs because they had two different set of rules to follow in their studies. The conventional courses engaged lot of energy which should have been spent for professional development in the ICT-ESP. The amount of competencies needed in the ICT-ESP for professional development was greater than those needed for any other ways of studying. The team entrepreneurs needed to develop skills in ICT, leadership and self-leadership, team development and entrepreneurship skills. The entrepreneurship skills included skills on marketing and sales, brand development, productization, and business administration. Considering the three-year time the team entrepreneurs spent in the ICT-ESP, the challenges were remarkable. Changes to the organization of IT Bachelor education are also suggested in the study. At first, it should be admitted that the ICT-ESP produces IT Bachelors with a different set of competencies compared to the conventional way of educating IT Bachelors. Secondly, the number of courses on general topics in mathematics, physics, and languages for team entrepreneurs studying in the ICTESP should be reconsidered and the conventional course-based teaching of the topics should be reorganized to support the team coaching process of the team entrepreneurs with their practiceoriented projects. Third, the upcoming team entrepreneurs should be equipped with relevant information about the ICT-ESP and what it would require in practice to study as a team entrepreneur. Finally, the upcoming team entrepreneurs should be carefully selected before they start in the ICT-ESP to have a possibility to eliminate solo players and those who have a too romantic view of being a team entrepreneur. The results gained in the study provided answers to the original research questions and the objectives of the study were met. Even though the IT degree programme was terminated during the research process, the amount of qualitative data gathered made it possible to justify the interpretations done.

Adaptive Markov chain Monte Carlo and Bayesian filtering for state space models

This thesis is concerned with the state and parameter estimation in state space models. The estimation of states and parameters is an important task when mathematical modeling is applied to many different application areas such as the global positioning systems, target tracking, navigation, brain imaging, spread of infectious diseases, biological processes, telecommunications, audio signal processing, stochastic optimal control, machine learning, and physical systems. In Bayesian settings, the estimation of states or parameters amounts to computation of the posterior probability density function. Except for a very restricted number of models, it is impossible to compute this density function in a closed form. Hence, we need approximation methods. A state estimation problem involves estimating the states (latent variables) that are not directly observed in the output of the system. In this thesis, we use the Kalman filter, extended Kalman filter, Gauss–Hermite filters, and particle filters to estimate the states based on available measurements. Among these filters, particle filters are numerical methods for approximating the filtering distributions of non-linear non-Gaussian state space models via Monte Carlo. The performance of a particle filter heavily depends on the chosen importance distribution. For instance, inappropriate choice of the importance distribution can lead to the failure of convergence of the particle filter algorithm. In this thesis, we analyze the theoretical Lᵖ particle filter convergence with general importance distributions, where p ≥2 is an integer. A parameter estimation problem is considered with inferring the model parameters from measurements. For high-dimensional complex models, estimation of parameters can be done by Markov chain Monte Carlo (MCMC) methods. In its operation, the MCMC method requires the unnormalized posterior distribution of the parameters and a proposal distribution. In this thesis, we show how the posterior density function of the parameters of a state space model can be computed by filtering based methods, where the states are integrated out. This type of computation is then applied to estimate parameters of stochastic differential equations. Furthermore, we compute the partial derivatives of the log-posterior density function and use the hybrid Monte Carlo and scaled conjugate gradient methods to infer the parameters of stochastic differential equations. The computational efficiency of MCMC methods is highly depend on the chosen proposal distribution. A commonly used proposal distribution is Gaussian. In this kind of proposal, the covariance matrix must be well tuned. To tune it, adaptive MCMC methods can be used. In this thesis, we propose a new way of updating the covariance matrix using the variational Bayesian adaptive Kalman filter algorithm.

Advanced analysis and design methods for preparative chromatographic separation processes

Preparative liquid chromatography is one of the most selective separation techniques in the fine chemical, pharmaceutical, and food industries. Several process concepts have been developed and applied for improving the performance of classical batch chromatography. The most powerful approaches include various single-column recycling schemes, counter-current and cross-current multi-column setups, and hybrid processes where chromatography is coupled with other unit operations such as crystallization, chemical reactor, and/or solvent removal unit. To fully utilize the potential of stand-alone and integrated chromatographic processes, efficient methods for selecting the best process alternative as well as optimal operating conditions are needed. In this thesis, a unified method is developed for analysis and design of the following singlecolumn fixed bed processes and corresponding cross-current schemes: (1) batch chromatography, (2) batch chromatography with an integrated solvent removal unit, (3) mixed-recycle steady state recycling chromatography (SSR), and (4) mixed-recycle steady state recycling chromatography with solvent removal from fresh feed, recycle fraction, or column feed (SSR–SR). The method is based on the equilibrium theory of chromatography with an assumption of negligible mass transfer resistance and axial dispersion. The design criteria are given in general, dimensionless form that is formally analogous to that applied widely in the so called triangle theory of counter-current multi-column chromatography. Analytical design equations are derived for binary systems that follow competitive Langmuir adsorption isotherm model. For this purpose, the existing analytic solution of the ideal model of chromatography for binary Langmuir mixtures is completed by deriving missing explicit equations for the height and location of the pure first component shock in the case of a small feed pulse. It is thus shown that the entire chromatographic cycle at the column outlet can be expressed in closed-form. The developed design method allows predicting the feasible range of operating parameters that lead to desired product purities. It can be applied for the calculation of first estimates of optimal operating conditions, the analysis of process robustness, and the early-stage evaluation of different process alternatives. The design method is utilized to analyse the possibility to enhance the performance of conventional SSR chromatography by integrating it with a solvent removal unit. It is shown that the amount of fresh feed processed during a chromatographic cycle and thus the productivity of SSR process can be improved by removing solvent. The maximum solvent removal capacity depends on the location of the solvent removal unit and the physical solvent removal constraints, such as solubility, viscosity, and/or osmotic pressure limits. Usually, the most flexible option is to remove solvent from the column feed. Applicability of the equilibrium design for real, non-ideal separation problems is evaluated by means of numerical simulations. Due to assumption of infinite column efficiency, the developed design method is most applicable for high performance systems where thermodynamic effects are predominant, while significant deviations are observed under highly non-ideal conditions. The findings based on the equilibrium theory are applied to develop a shortcut approach for the design of chromatographic separation processes under strongly non-ideal conditions with significant dispersive effects. The method is based on a simple procedure applied to a single conventional chromatogram. Applicability of the approach for the design of batch and counter-current simulated moving bed processes is evaluated with case studies. It is shown that the shortcut approach works the better the higher the column efficiency and the lower the purity constraints are.

Fever induction pathways: evidence from responses to systemic or local cytokine formation

The immune and central nervous systems are functionally connected and interacting. The concept that the immune signaling to the brain which induces fever during infection and inflammation is mediated by circulating cytokines has been traditionally accepted. Administration of bacterial lipopolysaccharide (LPS) induces the appearance of a so-termed "cytokine cascade" in the circulation more or less concomitantly to the developing febrile response. Also, LPS-like fever can be induced by systemic administration of key cytokines (IL-1ß, TNF-alpha, and others). However, anti-cytokine strategies against IL-1ß or TNF-alpha along with systemic injections of LPS frequently lead to attenuation of the later stages of the febrile response but not of the initial phase of fever, indicating that cytokines are rather involved in the maintenance than in the early induction of fever. Within the last years experimental evidence has accumulated indicating the existence of neural transport pathways of immune signals to the brain. Because subdiaphragmatic vagotomy prevents or attenuates fever in response to intraperitoneal or intravenous injections of LPS, a role for vagal afferent nerve fibers in fever induction has been proposed. Also other sensory nerves may participate in the manifestation of febrile responses under certain experimental conditions. Thus, injection of a small dose of LPS into an artificial subcutaneous chamber results in fever and formation of cytokines within the inflamed tissue around the site of injection. This febrile response can be blocked in part by injection of a local anesthetic into the subcutaneous chamber, indicating a participation of cutaneous afferent nerve signals in the manifestation of fever in this model. In conclusion, humoral signals and an inflammatory stimulation of afferent sensory nerves can participate in the generation and maintenance of a febrile response.