Glutathione and the redox control system trypanothione/trypanothione reductase are involved in the protection of Leishmania spp. against nitrosothiol-induced cytotoxicity

Glutathione is the major intracellular antioxidant thiol protecting mammalian cells against oxidative stress induced by oxygen- and nitrogen-derived reactive species. In trypanosomes and leishmanias, trypanothione plays a central role in parasite protection against mammalian host defence systems by recycling trypanothione disulphide by the enzyme trypanothione reductase. Although Kinetoplastida parasites lack glutathione reductase, they maintain significant levels of glutathione. The aim of this study was to use Leishmania donovani trypanothione reductase gene mutant clones and different Leishmania species to examine the role of these two individual thiol systems in the protection mechanism against S-nitroso-N-acetyl-D,L-penicillamine (SNAP), a nitrogen-derived reactive species donor. We found that the resistance to SNAP of different species of Leishmania was inversely correlated with their glutathione concentration but not with their total low-molecular weight thiol content (about 0.18 nmol/10(7) parasites, regardless Leishmania species). The glutathione concentration in L. amazonensis, L. donovani, L. major, and L. braziliensis were 0.12, 0.10, 0.08, and 0.04 nmol/10(7) parasites, respectively. L. amazonensis, that have a higher level of glutathione, were less susceptible to SNAP (30 and 100 µM). The IC50 values of SNAP determined to L. amazonensis, L. donovani, L. major, and L. braziliensis were 207.8, 188.5, 160.9, and 83 µM, respectively. We also observed that L. donovani mutants carrying only one trypanothione reductase allele had a decreased capacity to survive (~40%) in the presence of SNAP (30-150 µM). In conclusion, the present data suggest that both antioxidant systems, glutathione and trypanothione/trypanothione reductase, participate in protection of Leishmania against the toxic effect of nitrogen-derived reactive species.

Biomass Utilization in PFC Co-firing System with the Slagging and Fouling Analysis

Master’s thesis Biomass Utilization in PFC Co-firing System with the Slagging and Fouling Analysis is the study of the modern technologies of different coal-firing systems: PFC system, FB system and GF system. The biomass co-fired with coal is represented by the research of the company Alstom Power Plant. Based on the back ground of the air pollution, greenhouse effect problems and the national fuel security today, the bioenergy utilization is more and more popular. However, the biomass is promoted to burn to decrease the emission amount of carbon dioxide and other air pollutions, new problems form like slagging and fouling, hot corrosion in the firing systems. Thesis represent the brief overview of different coal-firing systems utilized in the world, and focus on the biomass-coal co-firing in the PFC system. The biomass supply and how the PFC system is running are represented in the thesis. Additionally, the new problems of hot corrosion, slagging and fouling are mentioned. The slagging and fouling problem is simulated by using the software HSC Chemistry 6.1, and the emissions comparison between coal-firing and co-firing are simulated as well.

Intensification of Operation of Inclined Plate Settler at Fertilizer Plant

Fertilizer plant’s process waters contain high concentrations of nitrogen compounds, such as ammonium and nitrate. Phosphorus and fluorine, which originate from phosphoric acid and rock phosphate (apatite) used in fertilizer production, are also present. Phosphorus and nitrogen are the primary nutrients causing eutrophication of surface waters. At fertilizer plant process waters are held in closed internal circulation. In a scrubber system process waters are used for washing exhaust gases from fertilizer reactors and dry gases from granulation drums as well as for cooling down the fertilizer slurry in neutralization reactor. Solids in process waters are separated in an inclined plate settler by gravitational sedimentation. However, the operation of inclined plate settler has been inadequate. The aim of this thesis was to intensify the operation of inclined plate settler and thus the solids separation e.g. through coagulation and/or flocculation process. Chemical precipitation was studied to reduce the amount of dissolved species in process waters. Specific interest was in precipitation of nitrogen, phosphorus, and fluorine containing specimens. Amounts of phosphorus and fluorine were reduced significantly by chemical precipitation. When compared to earlier studies, annual chemical costs were almost eight times lower. Instead, nitrogen compounds are readily dissolved in water, thus being difficult to remove by precipitation. Possible alternative techniques for nitrogen removal are adsorption, ion exchange, and reverse osmosis. Settling velocities of pH adjusted and flocculated process waters were sufficient for the operation of inclined plate settler. Design principles of inclined plate settler are also presented. In continuation studies, flow conditions in inclined plate settler should be modelled with computational fluid dynamics and suitability of adsorbents, ion exchange resins, and membranes should be studied in laboratory scale tests.

A carbohydrate-based mechanism of species recognition in sea urchin fertilization

In the present review, we describe a systematic study of the sulfated polysaccharides from marine invertebrates, which led to the discovery of a carbohydrate-based mechanism of sperm-egg recognition during sea urchin fertilization. We have described unique polymers present in these organisms, especially sulfated fucose-rich compounds found in the egg jelly coat of sea urchins. The polysaccharides have simple, linear structures consisting of repeating units of oligosaccharides. They differ among the various species of sea urchins in specific patterns of sulfation and/or position of the glycosidic linkage within their repeating units. These polysaccharides show species specificity in inducing the acrosome reaction in sea urchin sperm, providing a clear-cut example of a signal transduction event regulated by sulfated polysaccharides. This distinct carbohydrate-mediated mechanism of sperm-egg recognition coexists with the bindin-protein system. Possibly, the genes involved in the biosynthesis of these sulfated fucans did not evolve in concordance with evolutionary distance but underwent a dramatic change near the tip of the Strongylocentrotid tree. Overall, we established a direct causal link between the molecular structure of a sulfated polysaccharide and a cellular physiological event - the induction of the sperm acrosome reaction in sea urchins. Small structural changes modulate an entire system of sperm-egg recognition and species-specific fertilization in sea urchins. We demonstrated that sulfated polysaccharides - in addition to their known function in cell proliferation, development, coagulation, and viral infection - mediate fertilization, and respond to evolutionary mechanisms that lead to species diversity.

Participation of the cholinergic system in the ethanol-induced suppression of paradoxical sleep in rats

Sleep disturbance is among the many consequences of ethanol abuse in both humans and rodents. Ethanol consumption can reduce REM or paradoxical sleep (PS) in humans and rats, respectively. The first aim of this study was to develop an animal model of ethanol-induced PS suppression. This model administered intragastrically (by gavage) to male Wistar rats (3 months old, 200-250 g) 0.5 to 3.5 g/kg ethanol. The 3.5 g/kg dose of ethanol suppressed the PS stage compared with the vehicle group (distilled water) during the first 2-h interval (0-2 h; 1.3 vs 10.2; P < 0.001). The second aim of this study was to investigate the mechanisms by which ethanol suppresses PS. We examined the effects of cholinergic drug pretreatment. The cholinergic system was chosen because of the involvement of cholinergic neurotransmitters in regulating the sleep-wake cycle. A second set of animals was pretreated with 2.5, 5.0, and 10 mg/kg pilocarpine (cholinergic agonist) or atropine (cholinergic antagonist). These drugs were administered 1 h prior to ethanol (3.5 g/kg) or vehicle. Treatment with atropine prior to vehicle or ethanol produced a statistically significant decrease in PS, whereas pilocarpine had no effect on minutes of PS. Although the mechanism by which ethanol induces PS suppression is not fully understood, these data suggest that the cholinergic system is not the only system involved in this interaction.

Caspase dependence of the death of neonatal retinal ganglion cells induced by axon damage and induction of autophagy as a survival mechanism

We examined the degeneration of post-mitotic ganglion cells in ex-vivo neonatal retinal explants following axon damage. Ultrastructural features of both apoptosis and autophagy were detected. Degenerating cells reacted with antibodies specific for activated caspase-3 or -9, consistent with the presence of caspase activity. Furthermore, peptidic inhibitors of caspase-9, -6 or -3 prevented cell death (100 µM Ac-LEDH-CHO, 50 µM Ac-VEID-CHO and 10 µM Z-DEVD-fmk, respectively). Interestingly, inhibition of autophagy by 7-10 mM 3-methyl-adenine increased the rate of cell death. Immunohistochemistry data, caspase activation and caspase inhibition data suggest that axotomy of neonatal retinal ganglion cells triggers the intrinsic apoptotic pathway, which, in turn, is counteracted by a pro-survival autophagic response, demonstrated by electron microscopy profiles and pharmacological autophagy inhibitor.

Participation of the GABAergic system in the anesthetic effect of Lippia alba (Mill.) N.E. Brown essential oil

The objective of this study was to identify the possible involvement of the GABAergic system in the anesthetic effect of Lippia alba essential oil (EO). We propose a new animal model using silver catfish (Rhamdia quelen) exposed to an anesthetic bath to study the mechanism of action of EO. To observe the induction and potentiation of the anesthetic effect of EO, juvenile silver catfish (9.30 ± 1.85 g; 10.15 ± 0.95 cm; N = 6) were exposed to various concentrations of L. alba EO in the presence or absence of diazepam [an agonist of high-affinity binding sites for benzodiazepinic (BDZ) sites coupled to the GABA A receptor complex]. In another experiment, fish (N = 6) were initially anesthetized with the EO and then transferred to an anesthetic-free aquarium containing flumazenil (a selective antagonist of binding sites for BDZ coupled to the GABA A receptor complex) or water to assess recovery time from the anesthesia. In this case, flumazenil was used to observe the involvement of the GABA-BDZ receptor in the EO mechanism of action. The results showed that diazepam potentiates the anesthetic effect of EO at all concentrations tested. Fish exposed to diazepam and EO showed faster recovery from anesthesia when flumazenil was added to the recovery bath (12.0 ± 0.3 and 7.2 ± 0.7, respectively) than those exposed to water (9.2 ± 0.2 and 3.5 ± 0.3, respectively). In conclusion, the results demonstrated the involvement of the GABAergic system in the anesthetic effect of L. alba EO on silver catfish.

Influence of the dopaminergic system, CREB, and transcription factor-κB on cocaine neurotoxicity

Cocaine is a widely used drug and its abuse is associated with physical, psychiatric and social problems. Abnormalities in newborns have been demonstrated to be due to the toxic effects of cocaine during fetal development. The mechanism by which cocaine causes neurological damage is complex and involves interactions of the drug with several neurotransmitter systems, such as the increase of extracellular levels of dopamine and free radicals, and modulation of transcription factors. The aim of this review was to evaluate the importance of the dopaminergic system and the participation of inflammatory signaling in cocaine neurotoxicity. Our study showed that cocaine activates the transcription factors NF-κB and CREB, which regulate genes involved in cellular death. GBR 12909 (an inhibitor of dopamine reuptake), lidocaine (a local anesthetic), and dopamine did not activate NF-κB in the same way as cocaine. However, the attenuation of NF-κB activity after the pretreatment of the cells with SCH 23390, a D1 receptor antagonist, suggests that the activation of NF-κB by cocaine is, at least partially, due to activation of D1 receptors. NF-κB seems to have a protective role in these cells because its inhibition increased cellular death caused by cocaine. The increase in BDNF (brain-derived neurotrophic factor) mRNA can also be related to the protective role of both CREB and NF-κB transcription factors. An understanding of the mechanisms by which cocaine induces cell death in the brain will contribute to the development of new therapies for drug abusers, which can help to slow down the progress of degenerative processes.

BotCloud Detection System

Leveraging cloud services, companies and organizations can significantly improve their efficiency, as well as building novel business opportunities. Cloud computing offers various advantages to companies while having some risks for them too. Advantages offered by service providers are mostly about efficiency and reliability while risks of cloud computing are mostly about security problems. Problems with security of the cloud still demand significant attention in order to tackle the potential problems. Security problems in the cloud as security problems in any area of computing, can not be fully tackled. However creating novel and new solutions can be used by service providers to mitigate the potential threats to a large extent. Looking at the security problem from a very high perspective, there are two focus directions. Security problems that threaten service user’s security and privacy are at one side. On the other hand, security problems that threaten service provider’s security and privacy are on the other side. Both kinds of threats should mostly be detected and mitigated by service providers. Looking a bit closer to the problem, mitigating security problems that target providers can protect both service provider and the user. However, the focus of research community mostly is to provide solutions to protect cloud users. A significant research effort has been put in protecting cloud tenants against external attacks. However, attacks that are originated from elastic, on-demand and legitimate cloud resources should still be considered seriously. The cloud-based botnet or botcloud is one of the prevalent cases of cloud resource misuses. Unfortunately, some of the cloud’s essential characteristics enable criminals to form reliable and low cost botclouds in a short time. In this paper, we present a system that helps to detect distributed infected Virtual Machines (VMs) acting as elements of botclouds. Based on a set of botnet related system level symptoms, our system groups VMs. Grouping VMs helps to separate infected VMs from others and narrows down the target group under inspection. Our system takes advantages of Virtual Machine Introspection (VMI) and data mining techniques.

Experimentation on Wind Powered Hydraulic Heating System

It is common knowledge of the world’s dependency on fossil fuel for energy, its unsustainability on the long run and the changing trend towards renewable energy as an alternative energy source. This aims to cut down greenhouse gas emission and its impact on the rate of ecological and climatic change. Quite remarkably, wind energy has been one of many focus areas of renewable energy sources and has attracted lots of investment and technological advancement. The objective of this research is to explore wind energy and its application in household heating. This research aims at applying experimental approach in real time to study and verify a virtually simulated wind powered hydraulic house heating system. The hardware components comprise of an integrated hydraulic pump, flow control valve, hydraulic fluid and other hydraulic components. The system design and control applies hardware in-the-loop (HIL) simulation setup. Output signal from the semi-empirical turbine modelling controls the integrated motor to generate flow. Throttling the volume flow creates pressure drop across the valve and subsequently thermal power in the system to be outputted using a heat exchanger. Maximum thermal power is achieved by regulating valve orifice to achieve optimum system parameter. Savonius rotor is preferred for its low inertia, high starting torque and ease of design and maintenance characteristics, but lags in power efficiency. A prototype turbine design is used; with power output in range of practical Savonius turbine. The physical mechanism of the prototype turbine’s augmentation design is not known and will not be a focus in this study.

Enhancing Security of Linux OS against Administrators

Inside cyber security threats by system administrators are some of the main concerns of organizations about the security of systems. Since operating systems are controlled and managed by fully trusted administrators, they can negligently or intentionally break the information security and privacy of users and threaten the system integrity. In this thesis, we propose some solutions for enhancing the security of Linux OS by restricting administrators’ access to superuser’s privileges while they can still manage the system. We designed and implemented an interface for administrators in Linux OS called Linux Admins’ User Interface (LAUI) for managing the system in secure ways. LAUI along with other security programs in Linux like sudo protect confidentiality and integrity of users’ data and provide a more secure system against administrators’ mismanagement. In our model, we limit administrators to perform managing tasks in secure manners and also make administrators accountable for their acts. In this thesis we present some scenarios for compromising users’ data and breaking system integrity by system administrators in Linux OS. Then we evaluate how our solutions and methods can secure the system against these administrators’ mismanagement.

New threats - old routines : bureaucratic adaptability in the security policy environment

Within the framework of state security policy, the focus of this dissertation are the relations between how new security threats are perceived and the policy planning and bureaucratic implementation that are designed to address them. In addition, this thesis explores and studies some of the inertias that might exist in the core of the state apparatus as it addresses new threats and how these could be better managed. The dissertation is built on five thematic and interrelated articles highlighting different aspects of when new significant national security threats are detected by different governments until the threats on the policy planning side translate into protective measures within the society. The timeline differs widely between different countries and some key aspects of this process are also studied. One focus concerns mechanisms for adaptability within the Intelligence Community, another on the policy planning process within the Cabinet Offices/National Security Councils and the third focus is on the planning process and how policy is implemented within the bureaucracy. The issue of policy transfer is also analysed, revealing that there is some imitation of innovation within governmental structures and policies, for example within the field of cyber defence. The main findings of the dissertation are that this context has built-in inertias and bureaucratic seams found in most government bureaucratic machineries. As much of the information and planning measures imply security classification of the transparency and internal debate on these issues, alternative assessments become limited. To remedy this situation, the thesis recommends ways to improve the decision-making system in order to streamline the processes involved in making these decisions. Another special focus of the thesis concerns the role of the public policy think tanks in the United States as an instrument of change in the country’s national security decision-making environment, which is viewed from the perspective as being a possible source of new ideas and innovation. The findings in this part are based on unique interviews data on how think tanks become successful and influence the policy debate in a country such as the United States. It appears clearly that in countries such as the United States think tanks smooth the decision making processes, and that this model with some adaptations also might be transferrable to other democratic countries.

Suljetun sähkönjakeluverkon regulaatio teollisuusympäristössä

Tässä työssä tutkitaan suljetun jakeluverkon regulaatiota yhden suomalaisen teollisuussähköverkon näkökulmasta ja sitä verrataan olemassa olevaan energiaviraston jakeluverkkoja koskevaan säätelymalliin. Työssä tutkitaan verkkoyhtiön kehittämän säätelymallin toimivuutta ja sitä kuinka se täyttää hyvän valvontamallin ominaispiirteet. Tässä työssä ei ole tarkoituksena esittää uutta valvontamallia, vaan tutkia ja arvioida olemassa olevia malleja. Työssä käydään läpi olemassa oleva kolmannen valvontajakson regulaatiomalli sekä muutokset, joita on esitetty tuleville valvontakausille. Työssä taustoitetaan valvontatoimintaa myös yleisen talousteorian ja valvontateorioiden avulla. Tämän taustoituksen avulla tarkastellaan teollisuussähköverkkojen erityisiä ominaisuuksia ja edelleen tutkitun teollisuussähköverkon korkeita käyttövaatimuksia ja syitä tällaisille vaatimuksille. Verkkoyhtiön käyttämä tariffimalli kuvataan myös sen liittyessä sääntelyyn saumattomasti. Työssä todistettiin mallin toimivuus tämän kaltaisessa toimintaympäristössä, jossa käyntivarmuusvaatimus on erittäin korkea. Havainnoissa myös korostuu mallin pitkäjänteisyys ja ennustettavuus. Laskentaesimerkkien avulla arvioidaan liittymähinnoittelun kohtuullisuutta asiakkaalle ja mallin toimivuutta yleensä. Näissä tarkasteluissa havaittiin, että yleisellä tasolla liittymähinnoittelu on kohtuullista asiakkaalle ja se mahdollistaa asiakkaan pääomien tehokkaamman käytön kuin ilman verkkoyhtiötä. Kehittämiskohteina tuodaan esille keskeytyksistä aiheutuvien haittojen käsittely ja se, ettei tällaiseen verkkoympäristöön ole tällä hetkellä toimivaa mittaria, jolla voitaisiin arvioida kuinka hyvin verkkoyhtiö toimii.

Energy Management System for LVDC Island Networks

Recent developments in power electronics technology have made it possible to develop competitive and reliable low-voltage DC (LVDC) distribution networks. Further, islanded microgrids—isolated small-scale localized distribution networks— have been proposed to reliably supply power using distributed generations. However, islanded operations face many issues such as power quality, voltage regulation, network stability, and protection. In this thesis, an energy management system (EMS) that ensures efficient energy and power balancing and voltage regulation has been proposed for an LVDC island network utilizing solar panels for electricity production and lead-acid batteries for energy storage. The EMS uses the master/slave method with robust communication infrastructure to control the production, storage, and loads. The logical basis for the EMS operations has been established by proposing functionalities of the network components as well as by defining appropriate operation modes that encompass all situations. During loss-of-powersupply periods, load prioritizations and disconnections are employed to maintain the power supply to at least some loads. The proposed EMS ensures optimal energy balance in the network. A sizing method based on discrete-event simulations has also been proposed to obtain reliable capacities of the photovoltaic array and battery. In addition, an algorithm to determine the number of hours of electric power supply that can be guaranteed to the customers at any given location has been developed. The successful performances of all the proposed algorithms have been demonstrated by simulations.

Threat modeling a factory environment using Microsoft Security Development Lifecycle methodology

The number of security violations is increasing and a security breach could have irreversible impacts to business. There are several ways to improve organization security, but some of them may be difficult to comprehend. This thesis demystifies threat modeling as part of secure system development. Threat modeling enables developers to reveal previously undetected security issues from computer systems. It offers a structured approach for organizations to find and address threats against vulnerabilities. When implemented correctly threat modeling will reduce the amount of defects and malicious attempts against the target environment. In this thesis Microsoft Security Development Lifecycle (SDL) is introduced as an effective methodology for reducing defects in the target system. SDL is traditionally meant to be used in software development, principles can be however partially adapted to IT-infrastructure development. Microsoft threat modeling methodology is an important part of SDL and it is utilized in this thesis to find threats from the Acme Corporation’s factory environment. Acme Corporation is used as a pseudonym for a company providing high-technology consumer electronics. Target for threat modeling is the IT-infrastructure of factory’s manufacturing execution system. Microsoft threat modeling methodology utilizes STRIDE –mnemonic and data flow diagrams to find threats. Threat modeling in this thesis returned results that were important for the organization. Acme Corporation now has more comprehensive understanding concerning IT-infrastructure of the manufacturing execution system. On top of vulnerability related results threat modeling provided coherent views of the target system. Subject matter experts from different areas can now agree upon functions and dependencies of the target system. Threat modeling was recognized as a useful activity for improving security.