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Abstract Podocytes are highly specialized cells playing a key role in the filtration function of the kidney. A damaged podocyte ultrastructure is associated with a reorganization of the actin cytoskeleton and accompanied with a loss of adhesion to the glomerular basement membrane leading to proteinuria in many forms of glomerular diseases, e.g. nephrotic syndrome. If the first-line therapy with glucocorticoids fails, alternative immunosuppressive agents are used, which are known to have the potential to stabilize the actin cytoskeleton. A new option for preventing relapses in steroid dependent nephrotic syndrome is the monoclonal antibody rituximab, which, in addition to its B-cell depleting effect, is assumed to have direct effects on podocytes. We here provide data on the non-immunological off-target effects of the immunosuppressant rituximab on podocyte structure and dynamics in an in vitro puromycin aminonucleoside model of podocyte injury. A conditionally immortalized human podocyte cell line was used. Differentiated podocytes were treated with puromycin aminonucleoside and rituximab. Our studies focussed on analyzing the structure of the actin cytoskeleton, cellular adhesion and apoptosis using immunofluorescence staining and protein biochemistry methods. Treatment with rituximab resulted in a stabilization of podocyte actin stress fibers in the puromycin aminonucleoside model, leading to an improvement in cell adhesion. A lower apoptosis rate was observed after parallel treatment with puromycin aminonucleoside and rituximab visualized by reduced nuclear fragmentation. Consistent with this data, Western-blot analyses demonstrated that rituximab directly affects the caspase pathways by inhibiting the activation of Caspases-8, -9 and -3, suggesting that rituximab may inhibit apoptosis. In conclusion, our results indicate an important role of the immunosuppressant rituximab in terms of stability and morphogenesis of podocytes, involving apoptosis pathways. This could help to improve therapeutical concepts for patients with proteinuria mediated by diseased podocytes.

Economic interpretation of public value was elaborated in welfare theory and public choice literature. Nowadays public value describes the value that an organization contributes to society (Moore 1995). The authors discuss this definition and look for a more focused concept of value. The chaotic conditions can be defined according to chaos theory or as conditions of disorder. The authors show conditions for chaos’ situations. Even in situations that are characterized by deterministic model, the model solutions and public value may become unpredictable because of non-linear relations between variables or of initial conditions prevailing. Disorder situations occur in case of natural disasters, extreme population changes, economic crises, transformation situations and a breakdown of unions and national states. The difficulty to formulate public values are discussed for different kinds of disorders and evaluation schemes

One of the newer suggestions for the design of public economic units refers to Functional Overlapping Competing Jurisdictions (FOCJs), which are instruments to shape cooperation of jurisdictions, e.g. municipalities. The study clarifies important types of FOCJ. It concentrates on FOCJs where the members are municipalities. How useful such FOCJs are for designing public services depends on the composition of members, their decision concept of cooperation, the task of the FOCJ, the resources devoted to the FOCJ and the development phase of the FOCJ. For better understanding of those determinants, a microeconomic theory is needed. Therefore, the authors formulate models of FOCJ establishment, FOCJ operation and FOCJ competition for clients and members. The authors present already existing models and extensions of them based on the models in public choice and location theory, cooperation and game theory, and market theory to cover oligopolistic situations.

The authors discuss whether a small country with shrinking population should apply public enterprises to improve its economic situation for purposes of external economic relations policy. The study refers to Estonia as an example. Estonia has developed public enterprises of the central state and of the municipalities since the reestablishment of the Estonian Republic. As public enterprise use private forms of law, some management problems occur because public firms are legally obliged to practice the management by objectives. The operationalization of welfare maximisation or achievement of sustainability of society to formulate goals for public enterprises was yet not successful. However, public firms should increase income, avoid monopoly positions of private firms, provide special public services, and should realize public goals. The activities of Estonian public enterprises and their goals show that Estonian enterprises can be used as instruments for foreign trade. The authors formulate a simple two-country model comprising a small and a big country. They introduce a public interest function referring to production, demand and employment, which allows the authors to argue that under conditions of shrinking population, the small country’s public interests, becomes reduced. They show that employing public enterprises diminishes negative effects on public interests. Even some types of inefficient public firms may lead to improvements.

In order to develop Estonian policies of general education financing we analyze the prevailing regional distribution of general educational revenues and expenditures. Estonian per capita education funds are low and many small schools exist without a sufficient number of pupils. We consider two different basic strategies to improve the situation. The first strategy is an extension of a reform approach that has been performed since January 2008 that refers to the prevailing educational organization. It refers to improvements in financing schools. A state investment program was developed considering the number of pupils per municipality and special educational needs, but is not based on fair, equal treatment of particular cases. The second improvement strategy is based on the idea of FOCJ. The municipalities form FOCJ that are operating schools and negotiate with central government institutions for school equipment, salaries, loans etc. The theories of FOCJ-establishment, FOCJ-contribution determination and FOCJ-negotiations with central government are demonstrated. The FOCJ can supplement positively the first strategy of reform.

In many countries occur problems from unfunded mandates related to a shift of a function by an upper tier of government to lower rank governments without providing the lower one with financial means to perform these functions. The authors define the unfunded mandates and clarify how they relate to functions, uncovered costs and financial means of municipalities. Then they discuss the connexity principle in order to avoid unfunded mandates and respective functions variations in crises to avoid unfunded mandates. They point to conflicts which stem from allocation, stabilization and distribution activities. In Estonia the development of revenues and expenditures of central and local governments reflect tendencies to cause unfunded mandates especially in the period of crisis from 2009 to 2011. To fight unfunded mandates the connexity principle should be applied for municipal performance of central state functions and compulsory municipal functions. The central and local government finances should vary according to the principle of parallelism. If the total tax revenues vary the changes of block grants have to be parallel to the disposable incomes of the tiers of government.

Patients who have survived malignant melanoma for more than five years may lack the opportunity to talk about their burden. As a consequence their psychosocial care needs remain undetected and available supportive interventions may not be utilised. Therefore, the psychosocial burden of this patient group needs to be assessed using specific screening instruments. The aim of this study was to investigate the psychosocial burden of long-term melanoma survivors, their psychosocial care needs and the determinants of these needs. We wanted to find out if the use of professional support corresponds to the care needs defined by experts. Using the cancer registry of Rhineland-Palatinate, melanoma patients diagnosed at least 5 years before the survey were contacted by physicians. N = 689 former patients completed the Hornheide Questionnaire (short form HQ-S) to identify psychosocial support need (scale cut off ≥ 16 or item-based cut-off score) and the potential psychosocial determinants of these needs. Additionally, they were asked about their utilisation of the professional support system. More than one third (36%) of them was in need for professional psychosocial support. The highest burden scores concerned worry about tumour progression. Younger age (< 50), higher general fatigue, higher symptom burden, lower general health, negative social interactions and unfulfilled information needs were significant predictors of the need for psychosocial intervention. Related to the percentage of survivors identified as 'in need', the professional support system was underused. Further studies should investigate whether using the HQ-S to routinely identify burdened melanoma patients could lead to better fulfilment of their intervention needs, ultimately enhancing health-related quality of life.

AIM:The purpose of the study was to determine anxiety and depression, quality of life, and their determinants in long-term survivors of malignant melanoma. METHODS:In a state cancer registry a cohort of survivors of malignant melanoma was contacted via the physician registered. Of 1302 contactable patients, 689 (52.2%) completed a questionnaire including the Patient Health Questionnaire with generalized anxiety (GAD-7) and depression (PHQ-9) and the EORTC Quality of Life Questionnaire (EORTC QLQ 30). Based on multiple regression analysis, predictors of quality of life and distress were identified. Comparison data were assessed in two waves of representative face-to-face household surveys of the adult German population. RESULTS:An average of 8.4 (5.7 to 12.2) years after diagnosis, distress was higher in women compared to men and in middle adulthood (vs. older patients). Symptoms were higher in women than in men, and there was a decline of functioning and increase of symptoms across the age range of both genders. Compared to the general population, there were slightly increased depression and anxiety (only women), but no impaired global quality of life. Yet, survivors evidenced functional decline and more physical symptoms. Distress and reduced quality of life were consistently predicted by lack of social support, fear of recurrence, pessimism and self-blame. Distress was increased by a family history of melanoma, and additional mental and somatic diseases. CONCLUSION:Overall, long-term survivors have adjusted well achieving a global quality of life comparable to the general population. Yet, compromised functional dimensions, physical symptoms and distress indicate the need for integrating psychooncological screening into oncological follow-up, which might be guided by predictors such as family history or social support. Further prospective study is needed to determine the course of adaptation to the disease and corroborate the risk factors identified.

An H2O2 sensor for the application in industrial sterilisation processes has beendeveloped. Therefore, automated sterilisation equipment at laboratory scale has beenconstructed using parts from industrial sterilisation facilities. In addition, a software tool hasbeen developed for the control of the sterilisation equipment at laboratory scale. Firstmeasurements with the developed sensor set-up as part of the sterilisation equipment havebeen performed and the sensor has been physically characterised by optical microscopy andSEM.

The shrinking population during the break-down, adaptation and recovery phase in Estonian social and political development enforces municipal competition among the municipalities. Competition for inhabitants is embedded in regional competition showing horizontal and vertical competition relations. Inhabitants’ competition prevails indirectly through municipal business promotion competition and directly through competition for inhabitants. The competition shows three phases. A phase concerns zoning and long-term planning; a second one refers to negotiations with settlement firms and short-term actions to attract inhabitants followed by a phase of revisions of zoning and measures. The oligopolistic industrial zoning model of business promotion policy points to the consequences of horizontal municipal competition also on population. Vertical influences on business promotion policy demonstrate a game-theoretic example of intergovernmental intervention from higher government on zoning. The negotiation phase in business promotion policy is modelled by a bilateral monopoly model between a municipality and a settlement firm. Horizontal regional competition highlights the implications on inhabitants’ competition. An oligopoly model of direct inhabitant competition concerns the zoning in particular for housing. Furthermore, a model of public enterprise service and fee formation and of horizontal public firm competition shows inhabitants’ competition in the second phase. Forms of inhabitant competition concerning suburbanisation and using public debt, revenues such as taxes, fees and expenditures are mentioned. Finally, follows a discussion of possible instruments to regulate inhabitant competition.

Ausgehend vom Gesamtwerk Foucaults werden historisch entstandene Machtformen †die leviathanische Macht, die Panoptikummacht, die Pastoratsmacht und die Gouvernementalität erläutert und unterschieden. Beratung als Schlüsselform wird den jeweiligen Formen der Macht in ihren historischen Ausprägungen und Selbstverständnissen zugeordnet. Schließlich wird auf reflexive Haltungen in der Beratung, vor allem auf die parrhesia als machtkritische Form hingewiesen

The decision oriented theory of the public firm (Feng, Friedrich 2013) becomes extended. The authors consider that sometimes public firms compete horizontally as well. This can be due to competition among the public owners (e.g. municipalities) considering location choices for public firms they own, or public firms competing against each other. We mention some results related to the first type of competition and we refer to how the literature on location choices under oligopolic conditions could be referred to within the framework of our basic approach. One approach by Cornes and Hartley (2001) also allows modelling the establishment of joint ventures and their location choices. The basic model of the public firm is used to provide insight into the location choices of a trust of public firms. The trust exhibits coordination at three levels via the politically-oriented decision-making body of the public owner, the trust’s headquarters and subsidiary public firms. The resulting model illustrates the interplay of different decisionmakers and the effects of the coordinating activities. The first attempts to formulate a public firm decision-making oriented location theory exist.

Public firms are public economic units that take location decisions or are involved in such decisions. There is a lack of location theories that consider this feature. The literature on public facility location theory mainly concerns location of real capital serving economic units. Attempts to formulate a public firm decision-making oriented location theory are offered. Typical location factors of public firms relate to the goals of public firms, their environment and the number of decision-makers involved in the location decisions. A theory of the public firm is presented, that enables to develop a theory of location for public firms. It is introduced to industrial location theory and to location criteria based on investment rules. Its application in relation to public firms achieving welfare or public objectives is also covered. Interventions by the owner lead to more than one decision-maker and to principal agent models. Public firms compete horizontally due to competition among the public owners or public firms competing against each other. The authors mention some results on location choices within the framework of our basic approach.

Podocytes are highly differentiated kidney cells playing an important role in maintaining the glomerular filtration barrier. Particularly, the integrity of the actin cytoskeleton is crucial as cytoskeletal damage associated with foot process effacement and loss of slit diaphragms constitutes a major aspect of proteinuria. Previously, the mammalian target of rapamycin (mTOR) was linked to actin regulation and aberrant activity of the kinase was associated with renal disease. In this study, actin-related effects of mTOR inhibition by the immunosuppressant everolimus (EV) were investigated in human podocytes using an in vitro model of puromycin aminonucleoside (PAN) induced proteinuria. EV substantially recovered aberrant podocyte behavior by re-establishing a stationary phenotype with decreased migration efficiency, enhanced cell adhesion and recovery of actin stress fibers. Biochemical studies revealed substantial increase in the activity of RhoA and the effector pathway Rho-associated protein kinase (ROCK) and myosin light chain (MLC) by EV, all known regulators of stress fiber generation. Taken together, we show for the first time cytoskeleton stabilizing effects of the mTOR inhibitor EV and establish RhoA signaling as a key mediator in this process.

The share of GDP used for financing education in Estonia is somewhat lower in comparison to the EU average, the nominal amount of per capita education funds is much more lower due to a low level of economic development. Moreover, because of thin population per square km many small schools exist in Estonia without a sufficient number of pupils, which makes the education system more costly. We consider two different basic strategies to improve the situation. The current strategy of financing Estonian general education refers mainly to the prevailing educational and spatial organization. This strategy is not based on a fair equal treatment of cases. Therefore a new strategy of improvement of education financing system is discussed. It is based on the idea of Functional Overlapping Competitive Jurisdictions (FOCJ). The municipalities voluntarily form FOCJ that are operating schools. In this way municipalities may form a school jurisdiction that can negotiate with central government institutions for the loan and the school equipment etc. A municipality can act individually or the FOCJ negotiates for the municipal members in total. Theories of FOCJ-establishment, FOCJ-contribution determination and FOCJ-negotiations with central government are demonstrated. The FOCJ can supplement positively the first strategy of reform.

Calpain proteases drive intracellular signal transduction via specific proteolysis of multiple substrates upon Ca(2+)-induced activation. Recently, dUTPase, an enzyme essential to maintain genomic integrity, was identified as a physiological calpain substrate in Drosophila cells. Here we investigate the potential structural/functional significance of calpain-activated proteolysis of human dUTPase.Limited proteolysis of human dUTPase by mammalian m-calpain was investigated in the presence and absence of cognate ligands of either calpain or dUTPase. Significant proteolysis was observed only in the presence of Ca(II) ions, inducing calpain action. The presence or absence of the dUTP-analogue α,β-imido-dUTP did not show any effect on Ca(2+)-calpain-induced cleavage of human dUTPase. The catalytic rate constant of dUTPase was unaffected by calpain cleavage. Gel electrophoretic analysis showed that Ca(2+)-calpain-induced cleavage of human dUTPase resulted in several distinctly observable dUTPase fragments. Mass spectrometric identification of the calpain-cleaved fragments identified three calpain cleavage sites (between residues (4)SE(5); (7)TP(8); and (31)LS(32)). The cleavage between the (31)LS(32) peptide bond specifically removes the flexible N-terminal nuclear localization signal, indispensable for cognate localization.Results argue for a mechanism where Ca(2+)-calpain may regulate nuclear availability and degradation of dUTPase.

Estonian municipalities have to perform a broad range, while their fiscal resources are often limited in comparison to functions and large disparities in fiscal capacity prevail among them. Moreover, the power to regulate fiscal affairs is mostly in the hands of the central government. Municipalities do not possess satisfactory development planning perspectives. In particular municipalities in the North-East region and South Estonia have experienced considerable fiscal stress. We discuss how a strict application of the connexity principle can protect municipalities from the fiscal bottleneck. We also recommend the introduction of the principle of parallelism and investigate its effects on the down-flow grant system in Estonia. The procedure of determining the total sum of block grants needs to be changed. In most cases a high degree of parallelism applied when providing the unconditional grant via the equalization fund improves the fiscal stability and predictability of Estonian municipalities.

Under conditions of regional competition the authors discuss the role of the public sector in developing innovation activities and the ways to encourage innovation in the private and the public sector. Innovation policy gets linked to modern stage theories of development that focus on innovation. Estonia has reached the investment driven stage. With respect to several innovation indexes and measures of innovation policy a statistical comparison between Estonia and European Union member countries shows whether Estonia belongs to the group of leaders, renegades from leader role, losers or to that of aspirers. The indexes and indicators applied refer to the Community Innovation Survey, Summary Innovation Index, and Global Competitive Index. Although public higher education and R&D expenditures and co-operation of firms are above EU levels the analysis demonstrates that total R&D expenses are below European average. Co-operation between Universities and private firms is low and the number of patents as well. The knowledge creation and the ability to apply innovations enabled Estonia to reach an “aspirer position” whereas with respect to global competition Estonia possesses a “looser” position partly due to the lack of scientists, engineers, etc. Estonian public sector should develop and promote actively the necessary and promising fields of innovation analysed.