Dysregulated CD40-NF-kappaB signaling in the pathophysiology of aggressive non -Hodgkin's lymphoma B cells

Non-Hodgkin's Lymphomas (NHL) are a group (>30) of important human lymphoid cancers that unlike other tumors today, are showing a marked increase in incidence. The lack of insight to the pathogenesis of B-cell NHL poses a significant problem in the early detection and effective treatment of these malignancies. This study shows that large B-cell lymphoma (LBCL) cells, the most common type of B-cell NHL (account for more than 30% of cases), have developed a novel mechanism for autonomous neoplastic B cell growth. We have identified that the key transcription factor NF-κB, is constitutively activated in LBCL cell lines and primary biopsy-derived LBCL cells, suggesting that they are autonomously activated, and do not require accessory T-cell signaling for cell growth and survival. Further studies have indicated that LBCL cells ectopically express an important T-cell associated co-mitogenic factor, CD154 (CD40 ligand), that is able to internally activate the CD401NF-κB pathway, through constitutive binding to its cognate receptor, CD40, on the lymphoma cell surface. CD40 activation triggers the formation of a “Signalosome” comprising virtually the entire canonical CD40/NF-κB signaling pathway that is anchored by CD40 in plasma membrane lipid rafts. The CD40 Signalosome is vulnerable to interdiction by antibody against CD40 that disrupts the Signalosome and induces cell death in the malignant cells. In addition to constitutive NF-κB activation, we have found that the nuclear factor of activated T cells (NFAT) transcription factor is also constitutively activated in LBCL cells. We have demonstrated that the constitutively active NFATc1 and c-rel members of the NFAT and NF-κB families of transcription factors, respectively, interact with each other, bind to the CD154 promoter, and synergistically activate CD154 gene transcription. Down-regulation of NFATc1 and c-rel with small interfering RNA inhibits CD154 gene transcription and lymphoma cell growth. Our findings suggest that continuous CD40 activation not only provides dysregulated proliferative stimuli for lymphoma cell growth and extended tumor cell survival, but also allows continuous regeneration of the CD40 ligand in the lymphoma cell and thereby recharges the system through a positive feedback mechanism. Targeting the CD40/NF-κB signaling pathway could provide potential therapeutic modalities for LBCL cells in the future. ^

Advances in the Simultaneous Multiple Surface optical design method for imaging and non-imaging applications

Classical imaging optics has been developed over centuries in many areas, such as its paraxial imaging theory and practical design methods like multi-parametric optimization techniques. Although these imaging optical design methods can provide elegant solutions to many traditional optical problems, there are more and more new design problems, like solar concentrator, illumination system, ultra-compact camera, etc., that require maximum energy transfer efficiency, or ultra-compact optical structure. These problems do not have simple solutions from classical imaging design methods, because not only paraxial rays, but also non-paraxial rays should be well considered in the design process. Non-imaging optics is a newly developed optical discipline, which does not aim to form images, but to maximize energy transfer efficiency. One important concept developed from non-imaging optics is the “edge-ray principle”, which states that the energy flow contained in a bundle of rays will be transferred to the target, if all its edge rays are transferred to the target. Based on that concept, many CPC solar concentrators have been developed with efficiency close to the thermodynamic limit. When more than one bundle of edge-rays needs to be considered in the design, one way to obtain solutions is to use SMS method. SMS stands for Simultaneous Multiple Surface, which means several optical surfaces are constructed simultaneously. The SMS method was developed as a design method in Non-imaging optics during the 90s. The method can be considered as an extension to the Cartesian Oval calculation. In the traditional Cartesian Oval calculation, one optical surface is built to transform an input wave-front to an out-put wave-front. The SMS method however, is dedicated to solve more than 1 wave-fronts transformation problem. In the beginning, only 2 input wave-fronts and 2 output wave-fronts transformation problem was considered in the SMS design process for rotational optical systems or free-form optical systems. Usually “SMS 2D” method stands for the SMS procedure developed for rotational optical system, and “SMS 3D” method for the procedure for free-form optical system. Although the SMS method was originally employed in non-imaging optical system designs, it has been found during this thesis that with the improved capability to design more surfaces and control more input and output wave-fronts, the SMS method can also be applied to imaging system designs and possesses great advantage over traditional design methods. In this thesis, one of the main goals to achieve is to further develop the existing SMS-2D method to design with more surfaces and improve the stability of the SMS-2D and SMS-3D algorithms, so that further optimization process can be combined with SMS algorithms. The benefits of SMS plus optimization strategy over traditional optimization strategy will be explained in details for both rotational and free-form imaging optical system designs. Another main goal is to develop novel design concepts and methods suitable for challenging non-imaging applications, e.g. solar concentrator and solar tracker. This thesis comprises 9 chapters and can be grouped into two parts: the first part (chapter 2-5) contains research works in the imaging field, and the second part (chapter 6-8) contains works in the non-imaging field. In the first chapter, an introduction to basic imaging and non-imaging design concepts and theories is given. Chapter 2 presents a basic SMS-2D imaging design procedure using meridian rays. In this chapter, we will set the imaging design problem from the SMS point of view, and try to solve the problem numerically. The stability of this SMS-2D design procedure will also be discussed. The design concepts and procedures developed in this chapter lay the path for further improvement. Chapter 3 presents two improved SMS 3 surfaces’ design procedures using meridian rays (SMS-3M) and skew rays (SMS-1M2S) respectively. The major improvement has been made to the central segments selections, so that the whole SMS procedures become more stable compared to procedures described in Chapter 2. Since these two algorithms represent two types of phase space sampling, their image forming capabilities are compared in a simple objective design. Chapter 4 deals with an ultra-compact SWIR camera design with the SMS-3M method. The difficulties in this wide band camera design is how to maintain high image quality meanwhile reduce the overall system length. This interesting camera design provides a playground for the classical design method and SMS design methods. We will show designs and optical performance from both classical design method and the SMS design method. Tolerance study is also given as the end of the chapter. Chapter 5 develops a two-stage SMS-3D based optimization strategy for a 2 freeform mirrors imaging system. In the first optimization phase, the SMS-3D method is integrated into the optimization process to construct the two mirrors in an accurate way, drastically reducing the unknown parameters to only few system configuration parameters. In the second optimization phase, previous optimized mirrors are parameterized into Qbfs type polynomials and set up in code V. Code V optimization results demonstrates the effectiveness of this design strategy in this 2-mirror system design. Chapter 6 shows an etendue-squeezing condenser optics, which were prepared for the 2010 IODC illumination contest. This interesting design employs many non-imaging techniques such as the SMS method, etendue-squeezing tessellation, and groove surface design. This device has theoretical efficiency limit as high as 91.9%. Chapter 7 presents a freeform mirror-type solar concentrator with uniform irradiance on the solar cell. Traditional parabolic mirror concentrator has many drawbacks like hot-pot irradiance on the center of the cell, insufficient use of active cell area due to its rotational irradiance pattern and small acceptance angle. In order to conquer these limitations, a novel irradiance homogenization concept is developed, which lead to a free-form mirror design. Simulation results show that the free-form mirror reflector has rectangular irradiance pattern, uniform irradiance distribution and large acceptance angle, which confirm the viability of the design concept. Chapter 8 presents a novel beam-steering array optics design strategy. The goal of the design is to track large angle parallel rays by only moving optical arrays laterally, and convert it to small angle parallel output rays. The design concept is developed as an extended SMS method. Potential applications of this beam-steering device are: skylights to provide steerable natural illumination, building integrated CPV systems, and steerable LED illumination. Conclusion and future lines of work are given in Chapter 9. Resumen La óptica de formación de imagen clásica se ha ido desarrollando durante siglos, dando lugar tanto a la teoría de óptica paraxial y los métodos de diseño prácticos como a técnicas de optimización multiparamétricas. Aunque estos métodos de diseño óptico para formación de imagen puede aportar soluciones elegantes a muchos problemas convencionales, siguen apareciendo nuevos problemas de diseño óptico, concentradores solares, sistemas de iluminación, cámaras ultracompactas, etc. que requieren máxima transferencia de energía o dimensiones ultracompactas. Este tipo de problemas no se pueden resolver fácilmente con métodos clásicos de diseño porque durante el proceso de diseño no solamente se deben considerar los rayos paraxiales sino también los rayos no paraxiales. La óptica anidólica o no formadora de imagen es una disciplina que ha evolucionado en gran medida recientemente. Su objetivo no es formar imagen, es maximazar la eficiencia de transferencia de energía. Un concepto importante de la óptica anidólica son los “rayos marginales”, que se pueden utilizar para el diseño de sistemas ya que si todos los rayos marginales llegan a nuestra área del receptor, todos los rayos interiores también llegarán al receptor. Haciendo uso de este principio, se han diseñado muchos concentradores solares que funcionan cerca del límite teórico que marca la termodinámica. Cuando consideramos más de un haz de rayos marginales en nuestro diseño, una posible solución es usar el método SMS (Simultaneous Multiple Surface), el cuál diseña simultáneamente varias superficies ópticas. El SMS nació como un método de diseño para óptica anidólica durante los años 90. El método puede ser considerado como una extensión del cálculo del óvalo cartesiano. En el método del óvalo cartesiano convencional, se calcula una superficie para transformar un frente de onda entrante a otro frente de onda saliente. El método SMS permite transformar varios frentes de onda de entrada en frentes de onda de salida. Inicialmente, sólo era posible transformar dos frentes de onda con dos superficies con simetría de rotación y sin simetría de rotación, pero esta limitación ha sido superada recientemente. Nos referimos a “SMS 2D” como el método orientado a construir superficies con simetría de rotación y llamamos “SMS 3D” al método para construir superficies sin simetría de rotación o free-form. Aunque el método originalmente fue aplicado en el diseño de sistemas anidólicos, se ha observado que gracias a su capacidad para diseñar más superficies y controlar más frentes de onda de entrada y de salida, el SMS también es posible aplicarlo a sistemas de formación de imagen proporcionando una gran ventaja sobre los métodos de diseño tradicionales. Uno de los principales objetivos de la presente tesis es extender el método SMS-2D para permitir el diseño de sistemas con mayor número de superficies y mejorar la estabilidad de los algoritmos del SMS-2D y SMS-3D, haciendo posible combinar la optimización con los algoritmos. Los beneficios de combinar SMS y optimización comparado con el proceso de optimización tradicional se explican en detalle para sistemas con simetría de rotación y sin simetría de rotación. Otro objetivo importante de la tesis es el desarrollo de nuevos conceptos de diseño y nuevos métodos en el área de la concentración solar fotovoltaica. La tesis está estructurada en 9 capítulos que están agrupados en dos partes: la primera de ellas (capítulos 2-5) se centra en la óptica formadora de imagen mientras que en la segunda parte (capítulos 6-8) se presenta el trabajo del área de la óptica anidólica. El primer capítulo consta de una breve introducción de los conceptos básicos de la óptica anidólica y la óptica en formación de imagen. El capítulo 2 describe un proceso de diseño SMS-2D sencillo basado en los rayos meridianos. En este capítulo se presenta el problema de diseñar un sistema formador de imagen desde el punto de vista del SMS y se intenta obtener una solución de manera numérica. La estabilidad de este proceso se analiza con detalle. Los conceptos de diseño y los algoritmos desarrollados en este capítulo sientan la base sobre la cual se realizarán mejoras. El capítulo 3 presenta dos procedimientos para el diseño de un sistema con 3 superficies SMS, el primero basado en rayos meridianos (SMS-3M) y el segundo basado en rayos oblicuos (SMS-1M2S). La mejora más destacable recae en la selección de los segmentos centrales, que hacen más estable todo el proceso de diseño comparado con el presentado en el capítulo 2. Estos dos algoritmos representan dos tipos de muestreo del espacio de fases, su capacidad para formar imagen se compara diseñando un objetivo simple con cada uno de ellos. En el capítulo 4 se presenta un diseño ultra-compacto de una cámara SWIR diseñada usando el método SMS-3M. La dificultad del diseño de esta cámara de espectro ancho radica en mantener una alta calidad de imagen y al mismo tiempo reducir drásticamente sus dimensiones. Esta cámara es muy interesante para comparar el método de diseño clásico y el método de SMS. En este capítulo se presentan ambos diseños y se analizan sus características ópticas. En el capítulo 5 se describe la estrategia de optimización basada en el método SMS-3D. El método SMS-3D calcula las superficies ópticas de manera precisa, dejando sólo unos pocos parámetros libres para decidir la configuración del sistema. Modificando el valor de estos parámetros se genera cada vez mediante SMS-3D un sistema completo diferente. La optimización se lleva a cabo variando los mencionados parámetros y analizando el sistema generado. Los resultados muestran que esta estrategia de diseño es muy eficaz y eficiente para un sistema formado por dos espejos. En el capítulo 6 se describe un sistema de compresión de la Etendue, que fue presentado en el concurso de iluminación del IODC en 2010. Este interesante diseño hace uso de técnicas propias de la óptica anidólica, como el método SMS, el teselado de las lentes y el diseño mediante grooves. Este dispositivo tiene un límite teórica en la eficiencia del 91.9%. El capítulo 7 presenta un concentrador solar basado en un espejo free-form con irradiancia uniforme sobre la célula. Los concentradores parabólicos tienen numerosas desventajas como los puntos calientes en la zona central de la célula, uso no eficiente del área de la célula al ser ésta cuadrada y además tienen ángulos de aceptancia de reducido. Para poder superar estas limitaciones se propone un novedoso concepto de homogeneización de la irrandancia que se materializa en un diseño con espejo free-form. El análisis mediante simulación demuestra que la irradiancia es homogénea en una región rectangular y con mayor ángulo de aceptancia, lo que confirma la viabilidad del concepto de diseño. En el capítulo 8 se presenta un novedoso concepto para el diseño de sistemas afocales dinámicos. El objetivo del diseño es realizar un sistema cuyo haz de rayos de entrada pueda llegar con ángulos entre ±45º mientras que el haz de rayos a la salida sea siempre perpendicular al sistema, variando únicamente la posición de los elementos ópticos lateralmente. Las aplicaciones potenciales de este dispositivo son varias: tragaluces que proporcionan iluminación natural, sistemas de concentración fotovoltaica integrados en los edificios o iluminación direccionable con LEDs. Finalmente, el último capítulo contiene las conclusiones y las líneas de investigación futura.

Steric and mass-induced sea level variations in the Mediterranean Sea revisited

The total sea level variation (SLV) is the combination of steric and mass␣induced SLV, whose exact shares are key to understanding the oceanic response to climate system changes. Total SLV can be observed by radar altimetry satellites such as TOPEX/POSEIDON and Jason 1/2. The steric SLV can be computed through temperature and salinity profiles from in situ measurements or from ocean general circulation models (OGCM), which can assimilate the said observations. The mass-induced SLV can be estimated from its time-variable gravity (TVG) signals. We revisit this problem in the Mediterranean Sea estimating the observed, steric, and mass-induced SLV, for the latter we analyze the latest TVG data set from the GRACE (Gravity Recovery and Climate Experiment) satellite mission launched in 2002, which is 3.5 times longer than in previous studies, with the application of a two-stage anisotropic filter to reduce the noise in high-degree and -order spherical harmonic coefficients. We confirm that the intra-annual total SLV are only produced by water mass changes, a fact explained in the literature as a result of the wind field around the Gibraltar Strait. The steric SLV estimated from the residual of “altimetry minus GRACE” agrees in phase with that estimated from OGCMs and in situ measurements, although showing a higher amplitude. The net water fluxes through both the straits of Gibraltar and Sicily have also been estimated accordingly.

The End of the Transitional Period for Police and Criminal Justice Measures Adopted before the Lisbon Treaty: Who monitors trust in the European Criminal Justice area? CEPS Liberty and Security in Europe No. 74, December 2014

This study examines the legal and political implications of the forthcoming end of the transitional period for the measures in the fields of police and judicial cooperation in criminal matters, as set out in Protocol 36 to the EU Treaties. This Protocol limits some of the most far-reaching innovations introduced by the Treaty of Lisbon over EU cooperation on Justice and Home Affairs for a period of five years after the entry into force of the Treaty of Lisbon (until 1 December 2014), and provides the UK with special ‘opt out/opt-in’ possibilities. The study focuses on the meaning of the transitional period for the wider European Criminal Justice area. The most far-reaching change emerging from the end of this transition will be the expansion of the European Commission and Luxembourg Court of Justice scrutiny powers over Member States’ implementation of EU criminal justice law. The possibility offered by Protocol 36 for the UK to opt out and opt back in to pre-Lisbon Treaty instruments poses serious challenges to a common EU area of justice by further institutionalising ‘over-flexible’ participation in criminal justice instruments. The study argues that in light of Article 82 TFEU the rights of the defence are now inextricably linked to the coherency and effective operation of the principle of mutual recognition of criminal decisions, and calls the European Parliament to request the UK to opt in EU Directives on suspects procedural rights as condition for the UK to ‘opt back in’ measures like the European Arrest Warrant.

The Implementation, Application and Effects of the EU Directive on Copyright in the Information Society. CEPS Special Report No. 120, 19 November 2015

This study provides an ex-post evaluation of the EU copyright framework as provided by EU Directive 29/2001 on Copyright in the Information Society (InfoSoc Directive) and related legislation, focusing on four key criteria: effectiveness, efficiency, coherence and relevance. The evaluation finds that the EU copyright framework scores poorly on all four accounts. Of the four main goals pursued by the InfoSoc, only the alignment with international legislation can be said to have been fully achieved. The wider framework on copyright still generates costs by inhibiting content production, distribution and creation and generating productive, allocative and dynamic inefficiencies. Several problems also remain in terms of both internal and external coherence. Finally, espite its overall importance and relevance as a domain of legislation in the fields of content and media, the EU copyright framework is outdated in light of technological developments. Policy options to reform the current framework are provided in the CEPS companion study on the functioning and efficiency of the Digital Single Market in the field of copyright (CEPS Special Report No. 121/November 2015).

(Table 1) Number of invertebrate species per bottom trawl haul in the Kapp Norvegia to Halley Bay area on cruise EASIZ I (ANT-XIII/3) and in the Kapp Norvegia - Austasen area on cruise EASIZ III (ANT-XVII/3)

Ecological work carried out on the Antarctic and Magellan shelves since the first IBMANT conference held at the UMAG, Punta Arenas in 1997 is summarized to identify areas where progress has been made and others, where impor- tant gaps have remained in understanding past and present interaction between the Antarctic and the southern tip of South America. This information is complementary to a review on shallow-water work along the Scotia Arc (Barnes, 2005) and recent work done in the deep sea (Brandt and Hilbig, 2004). While principally referring to shipboard work in deeper water, above all during the recent international EASIZ and LAMPOS campaigns, relevant work from shore stations is also included. Six years after the first IBMANT symposium, significant progress has been made along the latitudinal gradient from the Magellan region to the high Antarctic in the fields of biodiversity, biogeography and community structure, life strategies and adaptations, the role of disturbance and its significance for biodiversity, and trophic coupling of the benthic realm with the water column and sea ice. A better understanding has developed of the role of evolutionary and ecological factors in shaping past and present-day environmental conditions, species composition and distribution, and ecosystem functioning. Furthermore, the science community engaged in unravelling Antarctic-Magellan interactions has advanced in methodological aspects such as new analytical approaches for comparing biodiversity derived from visual methods, growth and age determination, trophic modelling using stable isotope ratios, and molecular approaches for taxonomic and phylogenetic purposes. At the same time, much effort has been invested to complement the species inventory of the two adjacent regions. However, much work remains to be done to fill the numerous gaps. Some perspectives are outlined in this review, and sug- gestions are made where particular emphasis should be placed in future work, much of which will be developed in the frame of SCAR's EBA (Evolution and Biodiversity in the Antarctic) programme.

Optimization of facility location-allocation problem in customer-driven supply chain

This paper develops and applies an integrated multiple criteria decision making approach to optimize the facility location-allocation problem in the contemporary customer-driven supply chain. Unlike the traditional optimization techniques, the proposed approach, combining the analytic hierarchy process (AHP) and the goal programming (GP) model, considers both quantitative and qualitative factors, and also aims at maximizing the benefits of deliverer and customers. In the integrated approach, the AHP is used first to determine the relative importance weightings or priorities of alternative locations with respect to both deliverer oriented and customer oriented criteria. Then, the GP model, incorporating the constraints of system, resource, and AHP priority is formulated to select the best locations for setting up the warehouses without exceeding the limited available resources. In this paper, a real case study is used to demonstrate how the integrated approach can be applied to deal with the facility location-allocation problem, and it is proved that the integrated approach outperforms the traditional costbased approach.

Social policy in the UK

Social policy is a very complex area, and this chapter has only offered a brief summary of the most significant recent changes to the UK welfare state. Social policy expenditure has fluctuated over time, with considerable increases through the late 1990s and 2000s, but reductions planned in many areas by the current Coalition Government. The UK welfare state has slowly come to terms with women’s engagement in the labour market, but failed to overcome the persistent inequality between male and female incomes. While competition and choice have been introduced in many areas of the welfare state, their impacts have been varied and contested. Aside from health and education, UK social policy has become increasingly ‘residualised’, with many transfers now means-tested and services like social housing becoming less widely available. At the same time, however, different patterns can be observed across the UK, particularly in the fields of social care and education, where different arrangements apply in different nations. Future developments in social policy are likely to be shaped by the challenge of an ageing population, and the recently hardened public attitude towards particular groups of social policy beneficiaries.

Education and racism:a study of the teachers' and the pupils' relations in the schooling of black boys

This thesis examines the teachers' and the pupils' relations in the schooling of black boys. The study using the methodology of participant observation focusses on one school (Kilby) in an area of black population in an English city. The thesis’s intentions are two fold: firstly, in order to examine these relations, two major aspects of their interaction are addressed, that of the absence of teachers from conventional 'race-relations' research, and, the identification and examination of the anti-school pupils' sub-cultures. Two substantive questions are asked: what is the response of the teachers to the schooling of black pupils? and, what is the meaning of the pupils' resistance to schooling? Secondly, in attempting to answer these questions and offer a critique of the dominant 'race-relations' culturalist explanation of black youth's response to schooling, a theoretical framework has been developed which takes account of both the 'economic' and the 'sociological' perspectives. Methodology allowed and pointed to the importance of examining the teachers' ideologies and practices as well as those of the black boys. It is argued that a class analysis of the racially structured British society is more adequate than the conventional ethnic approach in explaining the black boys' location within Kilby School. Hence, it is posited that the major problem in the schooling of black youth is not that of their culture but of racism, which pervasively structures the social reality at Kilby school. Racism is mediated both through the existing institutional framework that discriminates against working-class youth and through the operation of race specific mechanisms, such as the process of racist stereotyping. It is thus further argued that the Kilby school teachers are of central causal significance to the - problems that the boys encounter. Furthermore, it is in response to these racist ideologies and practices that both West Indian and Asian pupils develop specific forms of collective resistance, which are seen to be linked to the wider black community, as legitimate strategies of survival.

A multinacionális vállalatok szerepe a hazai klaszterekben (Roles of multinational enterprises in the Hungarian clusters)

A cikk azt a kérdést vizsgálja, hogy milyen szerepet töltenek be a multinacionális vállalatok leányvállalatai a hazai klaszterekben, milyen a kapcsolatuk a klasztertag kis- és középvállalatokkal többek között a közös innovációban, a tudásközvetítésben, a klaszterek reputációjának növelésében. A felderítő kutatás a témát a hazai klaszterfejlesztési program, a Pólus Program által életre hívott három, úgynevezett akkreditált klaszter menedzsereivel, a klasztertag multinacionális vállalatok (MNV-k) hazai leányvállalatainak képviselőivel és a klasztertag KKV-k vezetőivel készült interjúk alapján mutatja be. A téma relevanciáját a program által potenciálisan indukált együttműködési folyamatok adják, mivel a klaszterfejlesztési pályázati konstrukciók úgy lettek kialakítva, hogy a klasztertag KKV-knak érdemes legyen nagyvállalatot is bevonniuk a közös innovációs és kutatás-fejlesztési projektekbe. A kutatási eredmények alapján az MNV leányvállalatainak leginkább a globális trendek és standardok klaszterbeli elterjesztésében van meghatározó szerepük, illetve a KKV-k és leányvállalatok közötti üzleti kapcsolatok alakításában kiemelt szerepe van a klasztermenedzsment szervezet tevékenységének. / === / The paper focuses on the topic which deals with the role of subsidiaries of multinational companies (MNC’s) in Hungarian industrial clusters in the fields of common innovation, knowledge transfer, and increasing the cluster’s reputation. The findings of the paper are based on an explorative research. Interviews were made with cluster managers, representatives of MNC’s subsidiaries, leaders of small and medium size (SME’s) enterprises operating in three accredited clusters created by the Hungarian cluster development program, the Pole Program. The relevance of the topic is given by the Program, which has induced potential cooperation between MNC’s subsidiaries and domestic SME’s in cluster environment in a way so the members of the cluster – SME’s and subsidiaries – were driven to cooperate in common innovation and R+D projects. The author’s research results suggest that MNC’s subsidiaries in Hungarian clusters seem to play a key role in the dissemination of global industrial trends and standards between the cluster members. The national cluster management organization can also play a decisive role in shaping business relationship between MNC’s and SME’s.

Biogeochemical factors affecting the fate and transport of mercury in the terrestrial environment at Oak Ridge, Tennessee

Mercury (Hg) contamination problem in the United Sates has been an important issue due to its potential threat to human and ecological health. This thesis presents a study of two Hg-contaminated sites along the East Fork Poplar Creek (EFPC) at Oak Ridge. The top soils from the terrestrial areas, along with the soils from three vertical soil horizons at the EFPC bank were sampled and analyzed for total-Hg (THg), methyl-Hg, total-organic-carbon (TOC), and pH. The stream bank soils were also analyzed for the stable-Hg-isotopes (198Hg, 199Hg, 200Hg, 201Hg, and 202Hg). Furthermore, some of the soil samples (n=7) from the same study sites were investigated for phytoavailability of mercury as measured by degree of Hg translocation in aboveground biomass of Impatiens walleriana plants grown in the soils.^ The results showed a significant difference (p<0.001) in THg concentrations for the forest soils (42.40±4.98 mg/kg) and the grassland soils (8.71±2.30 mg/kg). The higher THg and methyl-Hg concentrations were commensurate with the higher TOC content in the soils (p<0.001). Also, the THg concentrations for the upstream site was higher (129.08±34.14 mg/kg) than the downstream site (24.31±3.47 mg/kg). The two sites also differed in their stable Hg isotope compositions (p<0.001 for δ199Hg). The stable isotope analysis indicated the increased level of mass dependent isotopic fractionation with increasing depths along the EFPC bank. The difference between the two study sites was also prominent in case of the Hg uptake by the plants, with higher Hg uptake from the upstream soils compared to that from the downstream soils. A significant correlation, r=0.93 p<0.01, was observed between the Hg uptake and the soil-THg concentrations. THg was higher in the leaves (1161.87±310.01 μg/kg) than in the flowers (206.13±55.23 μg/kg) or the stems (634.54±403.35μg/kg). ^ The level of Hg contamination increased with decreasing distance from the point source and was highly influenced by plants/microbes, soil-organic-content, and Hg-speciation. The isotopic study indicated the existence of an additional Hg source in the EFPC watershed, possibly atmospheric Hg-deposition. These findings are worth taking into account while planning any Hg remediation effort and developing Hg loading criteria as per the National Pollutant Discharge Elimination System (NPDES) Program.^

The role of redox signaling in the molecular mechanism of tamoxifen resistance in breast cancer.

The emergence of tamoxifen or aromatase inhibitor resistance is a major problem in the treatment of breast cancer. The molecular signaling mechanism of antiestrogen resistance is not clear. Understanding the mechanisms by which resistance to these agents arise could have major clinical implications for preventing or circumventing it. Therefore, in this dissertation we have investigated the molecular mechanisms underlying antiestrogen resistance by studying the contributions of reactive oxygen species (ROS)-induced redox signaling pathways in antiestrogen resistant breast cancer cells. Our hypothesis is that the conversion of breast tumors to a tamoxifen-resistant phenotype is associated with a progressive shift towards a pro-oxidant environment of cells as a result of oxidative stress. The hypothesis of this dissertation was tested in an in vitro 2-D cell culture model employing state of the art biochemical and molecular techniques, including gene overexpression, immunoprecipitation, Western blotting, confocal imaging, ChIP, Real-Time RT-PCR, and anchorage-independent cell growth assays. We observed that tamoxifen (TAM) acts like both an oxidant and an antioxidant. Exposure of tamoxifen resistant LCC2 cell to TAM or 17 beta-estradiol (E2) induced the formation of reactive oxidant species (ROS). The formation of E2-induced ROS was inhibited by co-treatment with TAM, similar to cells pretreated with antioxidants. In LCC2 cells, treatments with either E2 or TAM were capable of inducing cell proliferation which was then inhibited by biological and chemical antioxidants. Exposure of LCC2 cells to tamoxifen resulted in a decrease in p27 expression. The LCC2 cells exposed to TAM showed an increase in p27 phosphorylation on T157 and T187. Conversely, antioxidant treatment showed an increase in p27 expression and a decrease in p27 phosphorylation on T157 and T187 in TAM exposed cells which were similar to the effects of Fulvestrant. In line with previous studies, we showed an increase in the binding of cyclin E-Cdk2 and in the level of p27 in TAM exposed cells that overexpressed biological antioxidants. Together these findings highly suggest that lowering the oxidant state of antiestrogen resistant LCC2 cells, increases LCC2 susceptibility to tamoxifen via the cyclin dependent kinase inhibitor p27.

Disciplining democracy: United Nations peacekeeping, international security and democratization in the post -Cold War era

After the end of the Cold War, democratization and good governance became the organizing concepts for activities of the United Nations, regional organizations and states in the fields of peace, development and security. How can this increasing interest in democratization and its connection with international security be explained? This dissertation applies the theoretical tools developed by Michel Foucault in his discussions of disciplinarity and government to the analysis of the United Nations debate on democracy in the 1990s, and of two United Nations pro-democracy peacekeeping operations and their aftermath: the United Nations interventions in Haiti and Croatia. It probes “how” certain techniques of power came into being and describes their effects, using as data the texts that elaborate the United Nations understanding of democracy and the texts that constitute peacekeeping. ^ In the face of the proliferation of unpredictable threats in the last decades of the twentieth century a new form of international power emerged. Order in the international arena increasingly was maintained through activities aimed at reducing risk and increasing predictability through the normalization of “rogue” states. The dissertation shows that in the context of these activities, which included but were not limited to UN peacekeeping, normality was identified with democracy, non-democratic regimes with international threats, and democratization with international security. “Good governance” doctrines translated the political debate on democracy into the technical language of functioning state institutions. International organizations adopted good governance as the framework that made democratization a universal task within the reach of their expertise. In Haiti, the United Nations engaged in efforts to transform punishment institutions (the judiciary, police and the prison) into disciplined and disciplinary machines. In Croatia, agreements signed in the context of peacekeeping established in detail the rules of functioning of administrations and the monitoring mechanisms for their implementation. However, in Haiti, the institutions promoted were not sustainable. And in Croatia reforms are stalled by lack of consensus. ^ This dissertation puts efforts to bring about democracy through peacekeeping in the context of a specific modality of power and suggests caution in engaging in universal normalizing endeavors. ^

Duration of a flood along a plant diversity gradient in the Jena Experiment (Main Experiment, June 2013)

The Jena Biodiversity Experiment is located on a Central European mesophilic floodplain on the banks of the Saale River (see further details below). In the main experiment, 82 grassland plots of 20 x 20 m were established from a pool of 60 species belonging to four functional groups (grasses, legumes, tall and small herbs). In May 2002, varying numbers of plant species from this species pool were sown in the plots to create a gradient of plant species richness (1, 2, 4, 8, 16 and 60 species) and functional richness (1, 2, 3, or 4 functional groups). Plots were maintained by bi-annual weeding and mowing. In June 2013, a natural 200-year flood event occurred at the field site. Rainfall in May 2013 in Jena was ~150mm, constituting >25% of annual precipitation at the site that year. Overall the flood affected the entire Elbe River Basin and much of Europe and was one of the largest natural flooding events in the past two centuries. The flood lasted for a total of 24 days at the site (30 May-24 June) and led to anaerobic soil conditions. Due to small topographical differences among the plots in the experiment (<1m), there was variation in the duration of flooding and the proportion of each plot that was flooded. This variation was well-distributed across the diversity gradient. To assess the importance of flood severity, the proportion of each plot that was flooded was estimated by eye (using five classes: 0 completely dry, 0.25 up to a quarter under water, 0.5 half, 0.75 up to three quarters under water, and 1 more than three quarters under water up to completely submerged). These values, for each of the 24 days that the flood lasted, were summed up to calculate a flooding index. The resulting flooding index is given for each plot of the Main Experiment.

Digital collaborations and entrepreneurship – the role of shareconomy and crowdsourcing in the era of smart city

The thesis begins with the classical cooperation and transfers it to the digital world. This work gives a detailed overview of the young fields of research smart city, shareconomy and crowdsourcing and links these fields with entrepreneurship. The core research aim is the finding of connections between the research fields smart city, shareconomy and crowdsourcing and entrepreneurial activities and the specific fields of application, success factors and conditions for entrepreneurs. The thesis consists of seven peer-reviewed publications. Based on primary and secondary data, the existence of entrepreneurial opportunities in the fields of smart city, shareconomy and crowdsourcing could be confirmed. The first part (publications 1-3) of the thesis are literature reviews to secure the fundamental base for further research. This part consists of newly created definitions and an extreme sharpening of the research fields for the near future. In the second part of the thesis (publications 4-7), empirical field work (in-depth interviews with entrepreneurs) and quantitative analyses (fuzzy set/qualitative comparative analysis and binary logistic regression analysis) contribute to the field of research with additional new insights. Summarizing, the insights are multi-layered: theoretical (e.g. new definitions, sharpening of the research field), methodical (e.g. first time application of the fuzzy set/qualitative comparative analysis in the field of crowdfunding) and qualitative (first time application of in-depth interviews with entrepreneurs in the fields of smart city and shareconomy). The global research question could be answered: the link between entrepreneurship and smart city, shareconomy and crowdfunding could be confirmed, concrete fields of application could be identified and further developments could be touched upon. This work strongly contributes to the young fields of research through much-needed basic work, new qualitative approaches, innovative methods and new insights and offers opportunities for discussion, criticism and support for further research.