In vivo fluctuation of Tax, Foxp3, CTLA-4, and GITR mRNA expression in CD4+CD25+ T cells of patients with human T-lymphotropic virus type 1-associated myelopathy

HTLV-1 Tax expression exerts an inhibitory effect on the Foxp3 transcription factor in CD4+CD25+ T-regulatory cells (Treg). For a better understanding of the role of Tax mRNA in the gene expression of cellular markers we measured Tax, Foxp3, CTLA-4, GITR, TGF-β, and IL-10 mRNA in Treg cells of 50 patients with human T-lymphotropic virus type 1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP; 27 women and 23 men; mean age: 56.7 years). The control group consisted of 23 non-infected subjects (12 women and 11 men) with a mean age of 51.3 years. Real-time PCR was used to measure mRNA of Tax proteins and several cellular markers of Treg function. Determinations revealed a high level of Tax mRNA in HAM/TSP (124.35 copies/100 CD4+CD25+ T cells). Foxp3, GITR, and CTLA-4 mRNA levels were lower in HAM/TSP patients (mean ± SD, 22.07 ± 0.78, 9.63 ± 0.36, and 4.54 ± 0.39, respectively) than in non-infected controls (47.15 ± 12.94, 22.14 ± 1.91, and 21.07 ± 2.31). Both groups had similar levels of TGF-β and IL-10. An inverse relationship was found between Tax levels and Foxp3, CTLA-4, and GITR levels. Conversely, there was a direct correlation between levels of Foxp3, GITR, and CTLA-4. Disease severity and evolution time did not correlate with Tax or Foxp3 levels. The present results suggest that Tax and Foxp3 mRNA vary with the same degree of disease severity in HAM/TSP patients. Tax fluctuations may affect CTLA-4 and GITR expression via the Foxp3 pathway, causing virus-induced dysfunction of CD4+CD25+ T cells in HAM/TSP patients.

Protection against neurotoxicity by an autophagic mechanism

The objective of the present study was to investigate the effects of 3-n-butylphthalide (NBP) on a 1-methyl-4-phenylpyridinium (MPP+)-induced cellular model of Parkinson’s disease (PD) and to illustrate the potential mechanism of autophagy in this process. For this purpose, rat PC12 pheochromocytoma cells were treated with MPP+ (1 mM) for 24 h following pretreatment with NBP (0.1 mM). Cell metabolic viability was determined by the MTT assay and cell ultrastructure was examined by transmission electron microscopy. The intracellular distribution and expression of α-synuclein and microtubule-associated protein light chain 3 (LC3) were detected by immunocytochemistry and Western blotting. Our results demonstrated that: 1) NBP prevented MPP+-induced cytotoxicity in PC12 cells by promoting metabolic viability. 2) NBP induced the accumulation of autophagosomes in MPP+-treated PC12 cells. 3) Further study of the molecular mechanism demonstrated that NBP enhanced the colocalization of α-synuclein and LC3 and up-regulated the protein level of LC3-II. These results demonstrate that NBP protects PC12 cells against MPP+-induced neurotoxicity by activating autophagy-mediated α-synuclein degradation, implying that it may be a potential effective therapeutic agent for the treatment of PD.

Role of high mobility group box-1 and protection of growth hormone and somatostatin in severe acute pancreatitis

In this study, we investigated the potential role of high-mobility group box 1 (HMGB1) in severe acute pancreatitis (SAP) and the effects of growth hormone (G) and somatostatin (S) in SAP rats. The rats were randomly divided into 6 groups of 20 each: sham-operated, SAP, SAP+saline, SAP+G, SAP+S and SAP+G+S. Ileum and pancreas tissues of rats in each group were evaluated histologically. HMGB1 mRNA expression was measured by reverse transcription-PCR. Levels of circulating TNF-α, IL-1, IL-6, and endotoxin were also measured. In the SAP group, interstitial congestion and edema, inflammatory cell infiltration, and interstitial hemorrhage occurred in ileum and pancreas tissues. The levels of HMGB1, TNF-α, IL-1, IL-6 and endotoxin were significantly up-regulated in the SAP group compared with those in the sham-operated group, and the 7-day survival rate was 0%. In the SAP+G and SAP+S groups, the inflammatory response of the morphological structures was alleviated, the levels of HMGB1, TNF-α, IL-1, IL-6, and endotoxin were significantly decreased compared with those in the SAP group, and the survival rate was increased. Moreover, in the SAP+G+S group, all histological scores were significantly improved and the survival rate was significantly higher compared with the SAP group. In conclusion, HMGB1 might participate in pancreas and ileum injury in SAP. Growth hormone and somatostatin might play a therapeutic role in the inflammatory response of SAP.

Brand Protection Perspectives

The main focus of this qualitative study is to explore and understand the boundaries of a brand protection program by assessing risks caused directly or indirectly by counterfeiting and finding remedies for treating those risks. 12 of 20 brand protection managers, anti-counterfeiting experts and marketing professors completed anonymously an internet-mediated questionnaire. During this study, a pattern of risk tolerance level within the sample was identified. The empirical results suggest that this pattern influences participants’ risk perception of and attitude towards counterfeiting; these also imply that, in risk treatment, this pattern influences decision- making as well as selection of countermeasures. Further, the results propose that brand equity and reputation are compared to other brand variables more vulnerable to the impact of counterfeiting. In addition, the results obtained in the question whether companies should employ public announcements of counterfeit seizures as an additional brand protection tool were contradictory. Companies were more apprehensive towards this solution than marketing professors. Thus, further investigation on this subject is recommended. This study concludes that as long as the impact of counterfeiting cannot be measured properly, the true damage on a brand or company and their reputation cannot be determined.

The influence of high cable penetration in distribution networks on earth fault currents and the operation of relay protection.

Recent Storms in Nordic countries were a reason of long power outages in huge territories. After these disasters distribution networks' operators faced with a problem how to provide adequate quality of supply in such situation. The decision of utilization cable lines rather than overhead lines were made, which brings new features to distribution networks. The main idea of this work is a complex analysis of medium voltage distribution networks with long cable lines. High value of cable’s specific capacitance and length of lines determine such problems as: high values of earth fault currents, excessive amount of reactive power flow from distribution to transmission network, possibility of a high voltage level at the receiving end of cable feeders. However the core tasks was to estimate functional ability of the earth fault protection and the possibility to utilize simplified formulas for operating setting calculations in this network. In order to provide justify solution or evaluation of mentioned above problems corresponding calculations were made and in order to analyze behavior of relay protection principles PSCAD model of the examined network have been created. Evaluation of the voltage rise in the end of a cable line have educed absence of a dangerous increase in a voltage level, while excessive value of reactive power can be a reason of final penalty according to the Finish regulations. It was proved and calculated that for this networks compensation of earth fault currents should be implemented. In PSCAD models of the electrical grid with isolated neutral, central compensation and hybrid compensation were created. For the network with hybrid compensation methodology which allows to select number and rated power of distributed arc suppression coils have been offered. Based on the obtained results from experiments it was determined that in order to guarantee selective and reliable operation of the relay protection should be utilized hybrid compensation with connection of high-ohmic resistor. Directional and admittance based relay protection were tested under these conditions and advantageous of the novel protection were revealed. However, for electrical grids with extensive cabling necessity of a complex approach to the relay protection were explained and illustrated. Thus, in order to organize reliable earth fault protection is recommended to utilize both intermittent and conventional relay protection with operational settings calculated by the use of simplified formulas.

Situational awareness for critical infrastructure protection

Postgraduate seminar series with a title Situational Awareness for Critical Infrastructure Protection held at the Department of Military Technology of the National Defence University in 2015. This book is a collection of some of talks that were presented in the seminar. The papers address designing inter-organizational situation awareness system, principles of designing for situation awareness, situation awareness in distributed teams, vulnerability analysis in a critical system context, tactical Command, Control, Communications, Computers, & Intelligence (C4I) systems, and improving situational awareness in the circle of trust. This set of papers tries to give some insight to current issues of the situation awareness for critical infrastructure protection. The seminar has always made a publication of the papers but this has been an internal publication of the Finnish Defence Forces and has not hindered publication of the papers in international conferences. Publication of these papers in peer reviewed conferences has indeed been always the goal of the seminar, since it teaches writing conference level papers. We still hope that an internal publication in the department series is useful to the Finnish Defence Forces by offering an easy access to these papers.

An evaluation of the 2003 tax reform effort in Brazil

This paper provides an assessment of the tax-reform effort launched by the newly elected Lula government in 2003. It analyzes how the envisaged reform had to be changed and scaled down, in the wake of strong political resistance, after a failed attempt to develop a consensual proposal, fully supported by state-governors. The main effective changes are then evaluated. Challenges ahead are discussed at the end.

Trophic cascades in boreal landscapes: top predator protection on tree seedlings and forest grouse

Changes in the abundance of top predators have brought about notable, cascading effects in ecosystems around the world. In this thesis, I examined several potential trophic cascades in boreal ecosystems, and their separate interspecific interactions. The main aim of the thesis was to investigate whether predators in the boreal forests have direct or indirect cascading effects on the lower trophic levels. First, I compared the browsing effects of different mammalian herbivores by excluding varying combinations of voles, hares and cervids from accessing the seedlings of silver birch (Betula pendula), Scots pine (Pinus sylvestris) and Norway spruce (Picea abies). Additionally, I studied the effect of simulated predation risk on vole browsing by using auditory cues of owls. Moving upwards on the trophic levels, I examined the intraguild interactions between the golden eagle (Aquila chrysaetos), and its mesopredator prey, the red fox (Vulpes vulpes) and the pine marten (Martes martes). To look at an entire potential trophic cascade, I further studied the combined impacts of eagles and mesopredators on the black grouse (Tetrao tetrix) and the hazel grouse (Tetrastes bonasia), predicting that the shared forest grouse prey would benefit from eagle presence. From the tree species studied, birch appears to be the most palatable one for the mammalian herbivores. I observed growth reductions in the presences of cervids and low survival associated with hares and voles, which suggests that they all weaken regeneration in birch stands. Furthermore, the simulated owl predation risk appeared to reduce vole browsing on birches in late summer, although the preferred grass forage is then old and less palatable. Browsing by voles and hares had a negative effect on the condition and survival of Scots pine, but in contrast, the impact of mammalian herbivores on spruce was found to be small, at least when more preferred food is available. I observed that the presence of golden eagles had a negative effect on the abundance of adult black grouse but a positive, protective effect on the proportion of juveniles in both black grouse and hazel grouse. Yet, this positive effect was not dependent on the abundance foxes or martens, nor did eagles seem to effectively decrease the abundance of these mesopredators. Conversely, the protection effect on grouse could arise from fear effects and also be mediated by other mesopredators. The results of this thesis provide important new information about trophic interactions in the boreal food webs. They highlight how different groups of mammalian herbivores vary in their effects on the growth and condition of different tree seedlings. Lowered cervid abundances could improve birch regeneration, which indirectly supports the idea that the key predators of cervids could cause cascading effects also in Fennoscandian forests. Owls seem to reduce vole browsing through an intimidation effect, which is a novel result of the cascading effects of owl vocalisation and could even have applications for protecting birch seedlings. In the third cascade examined in this thesis, I found the golden eagle to have a protective effect on the reproducing forest grouse, but it remains unclear through which smaller predators this effect is mediated. Overall, the results of this thesis further support the idea that there are cascading effects in the forests of Northern Europe, and that they are triggered by both direct and non‐lethal effects of predation.

A graphic explanation on how a tax on exports neutralizes the Dutch disease without costs to exporters

The adequate way of neutralizing the Dutch disease is the imposition of a variable tax on the export of the commodity that originates the disease. If such tax is equivalent to the "size" of the Dutch disease, it will shifts to the right its supply curve of the commodity in relation to the exchange rate, giving the existing domestic supply and the international demand, the exchange rate will depreciate at the value of the tax, and the equilibrium exchange rate will move from the "current" to the "industrial" equilibrium.

Relay protection in active distribution networks

Increasingly growing share of distributed generation in the whole electrical power system’s generating system is currently a worldwide tendency, driven by several factors, encircling mainly difficulties in refinement of megalopolises’ distribution networks and its maintenance; widening environmental concerns adding to both energy efficiency approaches and installation of renewable sources based generation, inherently distributed; increased power quality and reliability needs; progress in IT field, making implementable harmonization of needs and interests of different-energy-type generators and consumers. At this stage, the volume, formed by system-interconnected distributed generation facilities, have reached the level of causing broad impact toward system operation under emergency and post-emergency conditions in several EU countries, thus previously implementable approach of their preliminary tripping in case of a fault, preventing generating equipment damage and disoperation of relay protection and automation, is not applicable any more. Adding to the preceding, withstand capability and transient electromechanical stability of generating technologies, interconnecting in proximity of load nodes, enhanced significantly since the moment Low Voltage Ride-Through regulations, followed by techniques, were introduced in Grid Codes. Both aspects leads to relay protection and auto-reclosing operation in presence of distributed generation generally connected after grid planning and construction phases. This paper proposes solutions to the emerging need to ensure correct operation of the equipment in question with least possible grid refinements, distinctively for every type of distributed generation technology achieved its technical maturity to date and network’s protection. New generating technologies are equivalented from the perspective of representation in calculation of initial steady-state short-circuit current used to dimension current-sensing relay protection, and widely adopted short-circuit calculation practices, as IEC 60909 and VDE 0102. The phenomenon of unintentional islanding, influencing auto-reclosing, is addressed, and protection schemes used to eliminate an sustained island are listed and characterized by reliability and implementation related factors, whereas also forming a crucial aspect of realization of the proposed protection operation relieving measures.

Invoice-kaupan edut ja haitat verrattuna tavalliseen Tax Free kauppaan

Kandidaatintutkielmani käsittelee Invoice-kauppaa ja sitä, mitä etuja siihen liittyy verrattuna tavanomaiseen tax-free kauppaan. Invoice-veronpalautusjärjestelmässä EU:n ulkopuolella asuva asiakas saa veronpalautuksen samasta liikkeestä seuraavalla asiointikerralla. Arvonlisäveronpalautukset on kuitenkin haettava puolen vuoden sisällä ostosten tekemisestä. Tavanomaisessa tax-free kaupassa asiakas saa arvonlisäveronpalautuksen rajalta poistuessaan Suomesta. Invoicea käytettäessä asiakas saa verosta isomman osan takaisin kuin tavanomaisessa tax-free kaupassa, mutta palautuksen saaminen kestää kauemmin, koska Invoicea käytettäessä veronpalautuksen voi saada vain samasta liikkeestä, missä ostokset on tehty. Tutkielmani tarkastelee aihetta kauppiaan näkökulmasta. Kauppiaan kannalta Invoicen etuna on erityisesti asiakkaiden ”koukuttaminen”, koska veronpalautukset on aina haettava samasta liikkestä, mistä tuotteet on ostettu. Näin samat asiakkaat tulevat usein samaan liikkeeseen myös seuraavilla Suomen matkoilla saadakseen veronpalautukset. Tämä tuo liikkeille usein myös uusia kanta-asiakkaita.Toisaalta on huomioitava myös Invoicen käytöstä kauppiaalle ja kassoille mahdollisesti aiheutuva lisätyö ja kustannukset. Veronpalautusten maksaminen takaisin asiakkaille ja tullissa leimattujen kuittien käsittely vie kassoilla tavanomaista enemmän aikaa ja saattaa vaatia lisää henkilökuntaa. Tutkielma on toteutettu laadullisena eli kvalitatiivisena ja tutkimusmenetelmänä on käytetty haastatteluita. Haastateltavat ovat kauppiaita Kaakkois-Suomen alueelta. Tavoitteenani oli koota mahdollisimman monipuolinen haastateltavien joukko sisältäen niin vaate- ja vapaa-ajan liikkeitä kuin sekatavara- ja päivittäistavarakauppoja. Teorialähteinä käytin yliopiston kirjastosta lainattuja kirjoja, LUT:in tietokantojen ja Edilex-tietokannan artikkeleita sekä Verohallinnon dokumentteja ja verkkojulkaisuja. Lisäksi olen hyödyntänyt tutkielmassani myös ajankohtaisia uutisia sekä erilaisten paikallis- ja aikakauslehtien artikkeleita. Tutkielmani johtopäätöksissä tulin siihen tulokseen, että kauppiaan kannalta edullisinta on käyttää samanaikaisesti sekä Invoicea että perinteistä, palautusliikeiden palveluja hyödyntävää tax-free järjestelmää. Tämä mahdollistaa liikkeille mahdollisimman laajan asiakasjoukon. Suomessa usein käyvät ostosmatkailijat suosivat yleensä Invoicea täysimääräisen veronpalautuksen vuoksi. Palautusliikkeet taas veloittavat asiakkaalle maksettavasta veronpalautuksesta oman palvelumaksunsa. Suomessa harvemmin vieraileville taas palautusliikkeiden palvelut ovat edullisempia, sillä veronpalautukset saa rajalta maasta poistuttaessa, eikä tarvitse palata samaan liikkeeseen puolen vuoden sisällä. Palautusliikkeiden etuna Invoiceen nähden on myös asioinnin vaivattomuus, sillä eri liikkeissä asioivat ostosmatkailijat saavat kaikista matkalla tekemistään ostoksista arvonlisäveronpalautuksensa yhdestä paikasta sen sijaan, että kävisivät hakemassa ne joka liikkeestä erikseen.