Development of advanced tools and methods for the assessment and management of risk due to atypical major accident scenarios

Proper hazard identification has become progressively more difficult to achieve, as witnessed by several major accidents that took place in Europe, such as the Ammonium Nitrate explosion at Toulouse (2001) and the vapour cloud explosion at Buncefield (2005), whose accident scenarios were not considered by their site safety case. Furthermore, the rapid renewal in the industrial technology has brought about the need to upgrade hazard identification methodologies. Accident scenarios of emerging technologies, which are not still properly identified, may remain unidentified until they take place for the first time. The consideration of atypical scenarios deviating from normal expectations of unwanted events or worst case reference scenarios is thus extremely challenging. A specific method named Dynamic Procedure for Atypical Scenarios Identification (DyPASI) was developed as a complementary tool to bow-tie identification techniques. The main aim of the methodology is to provide an easier but comprehensive hazard identification of the industrial process analysed, by systematizing information from early signals of risk related to past events, near misses and inherent studies. DyPASI was validated on the two examples of new and emerging technologies: Liquefied Natural Gas regasification and Carbon Capture and Storage. The study broadened the knowledge on the related emerging risks and, at the same time, demonstrated that DyPASI is a valuable tool to obtain a complete and updated overview of potential hazards. Moreover, in order to tackle underlying accident causes of atypical events, three methods for the development of early warning indicators were assessed: the Resilience-based Early Warning Indicator (REWI) method, the Dual Assurance method and the Emerging Risk Key Performance Indicator method. REWI was found to be the most complementary and effective of the three, demonstrating that its synergy with DyPASI would be an adequate strategy to improve hazard identification methodologies towards the capture of atypical accident scenarios.

Pre-clinical and clinical development of leukemia stem cell inhibitors in acute leukemias

In Leukemias, recent developments have demonstrated that the Hedgehog pathway plays a key-role in the peculiar ability of self renewal of leukemia stem cells. The aim of this research activity was to investigate, through a first in man, Phase I, open label, clinical trial, the role and the impact, mainly in terms of safety profile, adverse events and pharmacokinetics, of a Sonic Hedgehog inhibitor compound on a population of heavely pretreated patients affected by AML, CML, MF, or MDS, resistant or refractory to standard chemotherapy. Thirty-five patients have been enrolled. The drug was administered orally, in 28 days cycles, without rest periods. The compound showed a good safety profile. The half life was of 17-35 hours, justifying the daily administration. Significant signs of activity, in terms of reduction of bone marrow blast cell amount were seen in most of the patients enrolled. Interestingly, correlative biological studies demonstrated that, comparing the gene expression profyiling signature of separated CD34+ cells before and after one cycle of treatment, the most variably expressed genes were involved in the Hh pathway. Moreover, we observed that many genes involved in MDR (multidrug resistance)were significantly down regulated after treatment. These data might lead to future clinical trials based on combinatory approaches, including, for instance, Hh inhibitors and conventional chemotherapy.

Cooperative Cognitive Wireless Networks over TV White and Gray Spaces

Wireless networks rapidly became a fundamental pillar of everyday activities. Whether at work or elsewhere, people often benefits from always-on connections. This trend is likely to increase, and hence actual technologies struggle to cope with the increase in traffic demand. To this end, Cognitive Wireless Networks have been studied. These networks aim at a better utilization of the spectrum, by understanding the environment in which they operate, and adapt accordingly. In particular recently national regulators opened up consultations on the opportunistic use of the TV bands, which became partially free due to the digital TV switch over. In this work, we focus on the indoor use of of TVWS. Interesting use cases like smart metering and WiFI like connectivity arise, and are studied and compared against state of the art technology. New measurements for TVWS networks will be presented and evaluated, and fundamental characteristics of the signal derived. Then, building on that, a new model of spectrum sharing, which takes into account also the height from the terrain, is presented and evaluated in a real scenario. The principal limits and performance of TVWS operated networks will be studied for two main use cases, namely Machine to Machine communication and for wireless sensor networks, particularly for the smart grid scenario. The outcome is that TVWS are certainly interesting to be studied and deployed, in particular when used as an additional offload for other wireless technologies. Seeing TVWS as the only wireless technology on a device is harder to be seen: the uncertainity in channel availability is the major drawback of opportunistic networks, since depending on the primary network channel allocation might lead in having no channels available for communication. TVWS can be effectively exploited as offloading solutions, and most of the contributions presented in this work proceed in this direction.

"Flirts and Other "Voluptuous Tyrants":Wollstonecraft, Rousseau and the Politics of Desire"

For the 18th and 19th centuries, flirtation was largely understood to be the symptom of a woman’s uncontrollable (and innate) sexual appetite. Any woman who questioned its cultural operations, such as Mary Wollstonecraft, was accused of being simultaneously sexually inappropriate in her interests, as well as prudish in her denial of feminine desire as a legitimate expression of a woman’s character. What this talk will argue, however, is that, for Wollstonecraft, the flirt is a fundamentally masculine figure who engages not in a struggle over desire, but rather in a struggle for power based on monarchical politics of the Ancien Regime.

Stratified Boston: The Brahmins, the Irish and the Boston Police Strike of 1919

This thesis explores the Boston Police Strike of 1919 through the lens of class struggle and ethnic tension. Through an examination of the development of Boston’s class structure, particularly focused on the upper class Brahmins and the Irish working class, it concludes that the Brahmins’ success in suppressing the police strikeallowed for their maintenance of socioeconomic power within the city despite their relatively small population. Based on their extreme class cohesion resulting from the growing prominence of Harvard University as well as the Brahmins’ unabashed discrimination against their ethnic neighbors in almost every sphere of society, theBrahmins were able to maintain their power in Boston’s cultural world. The Irish working class, on the other hand, which attempted to use the increasing popularity of public and police unionization to challenge the status and power of the Brahmins through the creation of the Boston Police Union and subsequently through the notorious Boston Police Strike of 1919 was ultimately unsuccessful, and it was left in the same position in which it started, at the bottom of the social ladder. The suppression of the strike by members of the upper class and their allies, particularly those in high government positions, served to preserve and affirm the socioeconomic power of the Brahmins over much of Boston society and brought the era of public police unionization to a close.

Nursing the fatherland? Hohenzollern statebuilding and the hidden transcript of political resistance in Hanoverian female charity during the Second German Empire

In summer 1866 the Austro-Prussian struggle for supremacy in Germany erupted into open conflict. King Georg V of Hanover sided with other governments loyal to the German Confederation against Prussia, but after initially defeating Prussian forces at Langensalza, he was forced to capitulate. Two days after the battle, on June 29, 1866, the widow of the Hanoverian general Sir Georg Julius von Hartmann told her daughter in no uncertain terms how she felt about the Prussian government and its allies. In her opinion they were nothing more than “robber states” that cloaked their disregard for the Ten Commandments in sanctimonious public displays of piety. “These Protestant Jesuits,” she continued, “offend me more than the Catholic ones. You know that I am German with all my heart and love my Germany, but I cannot consider them genuine Germans anymore because they only want to make Germany Prussian.”

Where Is "Home"? Value Conflicts, Identity Crises and the Formation of Cosmopolitan Identity in Myanmar Students Studying in the United States

Fully engaging in a new culture means translating oneself into a different set of cultural values, and many of the values can be foreign to the individual. The individual may face conflicting tensions between the psychological need to be a part of the new society and feelings of guilt or betrayal towards the former society, culture or self. Many international students from Myanmar, most of whom have little international experience, undergo this value and cultural translation during their time in American colleges. It is commonly assumed that something will be lost in the process of translation and that the students become more Westernized or never fit into both Myanmar and US cultures. However, the study of the narratives of the Myanmar students studying in the US reveals a more complex reality. Because individuals have multifaceted identities and many cultures and subcultures are fluctuating and intertwined with one another, the students¿ cross-cultural interactions can also help them acquire new ways of seeing things. Through their struggle to engage in the US college culture, many students display the theory of ¿cosmopolitanism¿ in their transformative identity formation process and thus, define and identify themselves beyond one set of cultural norms.

Romany Families in Romania: Intelligence and Personality of Children Cross-cultural and Specific Problems of Development

Psychogenetic research has emphasised the influence of social factors on a child's intellectual development. In her work, Ms. Dumitrascu examines two such factors; family size and order of birth. However, since these formal parameters tend to be unstable, other more informal factors should be taken into consideration. Of these, perhaps the most interesting is the "style" of parental education, which Ms. Dumitrascu regards as an expression of national traditions at the family level. This educational style is culture dependent. Only a comparative, cross-cultural study can reveal the real mechanism through which educational style influences the development of a child's intellect and personality. Ms. Dumitrascu conducted an experimental cross-cultural study aimed at examining the effects of the family environment on a child's intellectual development. Three distinct populations were involved in her investigation, each having quite a distinct status in their geographical area; Romanians, Romanies (Gypsies) from Romania, and Russians from the Republic of Moldova. She presented her research in the form of a series of articles written in English totalling 85 pages, and also on disc. A significant difference was revealed between the intelligence of a child living in a large family, and that of a child with no brothers or sisters. In the case of Romany children, the gap is remarkably large. Ms. Dumitrascu concludes that the simultaneous action of several negative factors (low socio-economic status, large family size, socio-cultural isolation of a population) may delay child development. Subjected to such a precarious environment, Romany children do not seek self-realisation, but rather struggle to survive the hardship. Most of them remain out of civilisation. Unfortunately, adult Romanies seldom express any concern regarding their children's successful social integration. The school as main socialisation tool has no value for most parents. Ms. Dumitrascu argues the need for a major effort aimed at helping Romany's social integration. She hopes this project will be of some help for psychologists, social workers, teachers, and all those who are interested in the integration into society of minority groups.

A Transformation of the Philosophical Thought of West European Liberalism in the Multi-National Central and South-Eastern European Milieu

This work was devoted to individual child development. Psychogenetic research has emphasised the importance of social factors in children's intellectual development and two social factors are looked at here, family size and birth order. The effect of the formal parameters is, however, very unstable and they should therefore be considered together with certain informal factors. Of these, parental educational style, which is an expression of national traditions at the family level, is of particular interest. Educational style is culture-dependent and only a comparative cross-cultural study can reveal the real mechanisms through which educational style influences children's intellectual and personality development. Dumitrascu carried out an experimental cross-cultural study dedicated to the effects of family environment on child intellectual development. This involved three distinct populations, each of which has a distinct status in their geographical area, namely Romanians, Romanies from Romania, and Russians from the Republic of Moldova. It showed a significant difference between child intelligence in those from large families and in only children, with a huge gap in the case of Romany children. This suggests that the simultaneous action of several negative factors (low socio-economic status, large family size, socio-cultural isolation of the population) may delay a child's development. Subjected to such a precarious environment, Romany children do not seek self-realisation but rather struggle to overcome hardship and the majority remain outside civilisation. Unfortunately, adult Romanies rarely show concern about their children's successful social integration, placing no value on the school as a major socialising tool. This leads to the conclusion that a major effort is needed to help Romanies' social integration.

The Dynamics of the Policies of Ethnic Cleansing in Silesia in the Nineteenth and Twentieth Centuries

Through studying German, Polish and Czech publications on Silesia, Mr. Kamusella found that most of them, instead of trying to objectively analyse the past, are devoted to proving some essential "Germanness", "Polishness" or "Czechness" of this region. He believes that the terminology and thought-patterns of nationalist ideology are so deeply entrenched in the minds of researchers that they do not consider themselves nationalist. However, he notes that, due to the spread of the results of the latest studies on ethnicity/nationalism (by Gellner, Hobsbawm, Smith, Erikson Buillig, amongst others), German publications on Silesia have become quite objective since the 1980s, and the same process (impeded by under funding) has been taking place in Poland and the Czech Republic since 1989. His own research totals some 500 pages, in English, presented on disc. So what are the traps into which historians have been inclined to fall? There is a tendency for them to treat Silesia as an entity which has existed forever, though Mr. Kamusella points out that it emerged as a region only at the beginning of the 11th century. These same historians speak of Poles, Czechs and Germans in Silesia, though Mr. Kamusella found that before the mid-19th century, identification was with an inhabitant's local area, religion or dynasty. In fact, a German national identity started to be forged in Prussian Silesia only during the Liberation War against Napoleon (1813-1815). It was concretised in 1861 in the form of the first Prussian census, when the language a citizen spoke was equated with his/her nationality. A similar census was carried out in Austrian Silesia only in 1881. The censuses forced the Silesians to choose their nationality despite their multiethnic multicultural identities. It was the active promotion of a German identity in Prussian Silesia, and Vienna's uneasy acceptance of the national identities in Austrian Silesia which stimulated the development of Polish national, Moravian ethnic and Upper Silesian ethnic regional identities in Upper Silesia, and Polish national, Czech national, Moravian ethnic and Silesian ethnic identities in Austrian Silesia. While traditional historians speak of the "nationalist struggle" as though it were a permanent characteristic of Silesia, Mr. Kamusella points out that such a struggle only developed in earnest after 1918. What is more, he shows how it has been conveniently forgotten that, besides the national players, there were also significant ethnic movements of Moravians, Upper Silesians, Silesians and the tutejsi (i.e. those who still chose to identify with their locality). At this point Mr. Kamusella moves into the area of linguistics. While traditionally historians have spoken of the conflicts between the three national languages (German, Polish and Czech), Mr Kamusella reminds us that the standardised forms of these languages, which we choose to dub "national", were developed only in the mid-18th century, after 1869 (when Polish became the official language in Galicia), and after the 1870s (when Czech became the official language in Bohemia). As for standard German, it was only widely promoted in Silesia from the mid 19th century onwards. In fact, the majority of the population of Prussian Upper Silesia and Austrian Silesia were bi- or even multilingual. What is more, the "Polish" and "Czech" Silesians spoke were not the standard languages we know today, but a continuum of West-Slavic dialects in the countryside and a continuum of West-Slavic/German creoles in the urbanised areas. Such was the linguistic confusion that, from time to time, some ethnic/regional and Church activists strove to create a distinctive Upper Silesian/Silesian language on the basis of these dialects/creoles, but their efforts were thwarted by the staunch promotion of standard German, and after 1918, of standard Polish and Czech. Still on the subject of language, Mr. Kamusella draws attention to a problem around the issue of place names and personal names. Polish historians use current Polish versions of the Silesian place names, Czechs use current Polish/Czech versions of the place names, and Germans use the German versions which were in use in Silesia up to 1945. Mr. Kamusella attempted to avoid this, as he sees it, nationalist tendency, by using an appropriate version of a place name for a given period and providing its modern counterpart in parentheses. In the case of modern place names he gives the German version in parentheses. As for the name of historical figures, he strove to use the name entered on the birth certificate of the person involved, and by doing so avoid such confusion as, for instance, surrounds the Austrian Silesian pastor L.J. Sherschnik, who in German became Scherschnick, in Polish, Szersznik, and in Czech, Sersnik. Indeed, the prospective Silesian scholar should, Mr. Kamusella suggests, as well as the three languages directly involved in the area itself, know English and French, since many documents and books on the subject have been published in these languages, and even Latin, when dealing in depth with the period before the mid-19th century. Mr. Kamusella divides the policies of ethnic cleansing into two categories. The first he classifies as soft, meaning that policy is confined to the educational system, army, civil service and the church, and the aim is that everyone learn the language of the dominant group. The second is the group of hard policies, which amount to what is popularly labelled as ethnic cleansing. This category of policy aims at the total assimilation and/or physical liquidation of the non-dominant groups non-congruent with the ideal of homogeneity of a given nation-state. Mr. Kamusella found that soft policies were consciously and systematically employed by Prussia/Germany in Prussian Silesia from the 1860s to 1918, whereas in Austrian Silesia, Vienna quite inconsistently dabbled in them from the 1880s to 1917. In the inter-war period, the emergence of the nation-states of Poland and Czechoslovakia led to full employment of the soft policies and partial employment of the hard ones (curbed by the League of Nations minorities protection system) in Czechoslovakian Silesia, German Upper Silesia and the Polish parts of Upper and Austrian Silesia. In 1939-1945, Berlin started consistently using all the "hard" methods to homogenise Polish and Czechoslovakian Silesia which fell, in their entirety, within the Reich's borders. After World War II Czechoslovakia regained its prewar part of Silesia while Poland was given its prewar section plus almost the whole of the prewar German province. Subsequently, with the active involvement and support of the Soviet Union, Warsaw and Prague expelled the majority of Germans from Silesia in 1945-1948 (there were also instances of the Poles expelling Upper Silesian Czechs/Moravians, and of the Czechs expelling Czech Silesian Poles/pro-Polish Silesians). During the period of communist rule, the same two countries carried out a thorough Polonisation and Czechisation of Silesia, submerging this region into a new, non-historically based administrative division. Democratisation in the wake of the fall of communism, and a gradual retreat from the nationalist ideal of the homogeneous nation-state with a view to possible membership of the European Union, caused the abolition of the "hard" policies and phasing out of the "soft" ones. Consequently, limited revivals of various ethnic/national minorities have been observed in Czech and Polish Silesia, whereas Silesian regionalism has become popular in the westernmost part of Silesia which remained part of Germany. Mr. Kamusella believes it is possible that, with the overcoming of the nation-state discourse in European politics, when the expression of multiethnicity and multilingualism has become the cause of the day in Silesia, regionalism will hold sway in this region, uniting its ethnically/nationally variegated population in accordance with the principle of subsidiarity championed by the European Union.

Panel 5: Memories and Fantasies of Genocides

Panel 5: Memories and Fantasies of Genocides Mark Hobbs, University of Winchester, United Kingdom: "Destroying Memory: The Attack on Holocaust Conscience and Memory in Britain 1942-2011" Download paper (login required) Kristen Dyck, Washington State University: "Hate Rock: White-Power Music in International Perspective" Download paper (login required) Audrey Mallet, Concordia University, Canada: “The Old Jewish Strangler and Other Ghost Stories: Poles’ Struggle to Come to Terms with the Holocaust” Download paper (login required) Tea Rozman-Clark, University of Nova Gorica, Slovenia: “Oral History: UN Peacekeepers and Local Population of the UN Safe Area Srebrenica” Download paper (login required) Chair: Kimberly Partee and Kathrin Haurand, Clark UniversityComment: Cecilie Felicia Stokholm Banke, Danish Institute for International Studies, Copenhagen

C/EBPalpha and the pathophysiology of acute myeloid leukemia

PURPOSE OF REVIEW: The transcription factor C/EBPalpha controls differentiation and proliferation in normal granulopoiesis in a stage-specific manner. Loss of C/EBPalpha function in myeloid cells in vitro and in vivo leads to a block to myeloid differentiation similar to that which is observed in malignant cells from patients with acute myeloid leukemia. The finding of C/EBPalpha alterations in subgroups of acute myeloid leukemia patients suggests a direct link between critically decreased C/EBPalpha function and the development of the disorder. RECENT FINDINGS: Conditional mouse models provide direct evidence that loss of C/EBPalpha function leads to the accumulation of myeloid blasts in the bone marrow. Targeted disruption of the wild type C/EBPalpha protein, while conserving the dominant-negative 30 kDa isoform of C/EBPalpha, induces an AML-like disease in mice. In hematopoietic stem cells C/EBPalpha serves to limit cell self-renewal. Finally, C/EBPalpha function is disrupted at different levels in specific subgroups of acute myeloid leukemia patients. SUMMARY: There is evidence that impaired C/EBPalpha function contributes directly to the development of acute myeloid leukemia. Normal myeloid development and acute myeloid leukemia are now thought to reflect opposite sides of the same hematopoietic coin. Restoring C/EBPalpha function represents a promising target for novel therapeutic strategies in acute myeloid leukemia.

In utero haematopoietic stem cell transplantation. Experiences in mice, sheep and humans

Early prenatal diagnosis and in utero therapy of certain fetal diseases have the potential to reduce fetal morbidity and mortality. The intrauterine transplantation of stem cells provides in some instances a therapeutic option before definitive organ failure occurs. Clinical experiences show that certain diseases, such as immune deficiencies or inborn errors of metabolism, can be successfully treated using stem cells derived from bone marrow. However, a remaining problem is the low level of engraftment that can be achieved. Efforts are made in animal models to optimise the graft and study the recipient's microenvironment to increase long-term engraftment levels. Our experiments in mice show similar early homing of allogeneic and xenogeneic stem cells and reasonable early engraftment of allogeneic murine fetal liver cells (17.1% donor cells in peripheral blood 4 weeks after transplantation), whereas xenogeneic HSC are rapidly diminished due to missing self-renewal and low differentiation capacities in the host's microenvironment. Allogeneic murine fetal liver cells have very good long-term engraftment (49.9% donor cells in peripheral blood 16 weeks after transplantation). Compared to the rodents, the sheep model has the advantage of body size and gestation comparable to the human fetus. Here, ultrasound-guided injection techniques significantly decreased fetal loss rates. In contrast to the murine in utero model, the repopulation capacities of allogeneic ovine fetal liver cells are lower (0.112% donor cells in peripheral blood 3 weeks after transplantation). The effect of MHC on engraftment levels seems to be marginal, since no differences could be observed between autologous and allogeneic transplantation (0.117% donor cells vs 0.112% donor cells in peripheral blood 1 to 2 weeks after transplantation). Further research is needed to study optimal timing and graft composition as well as immunological aspects of in utero transplantation.

Phenotypic and functional analysis of human fetal liver hematopoietic stem cells in culture

Steady-state hematopoiesis and hematopoietic transplantation rely on the unique potential of stem cells to undergo both self-renewal and multilineage differentiation. Fetal liver (FL) represents a promising alternative source of hematopoietic stem cells (HSCs), but limited by the total cell number obtained in a typical harvest. We reported that human FL nonobese diabetic/severe combined immunodeficient (NOD/SCID) repopulating cells (SRCs) could be expanded under simple stroma-free culture conditions. Here, we sought to further characterize FL HSC/SRCs phenotypically and functionally before and following culture. Unexpanded or cultured FL cell suspensions were separated into various subpopulations. These were tested for long-term culture potential and for in vivo repopulating function following transplantation into NOD/SCID mice. We found that upon culture of human FL cells, a tight association between classical stem cell phenotypes, such as CD34(+) /CD38(-) and/or side population, and NOD/SCID repopulating function was lost, as observed with other sources. Although SRC activity before and following culture consistently correlated with the presence of a CD34(+) cell population, we provide evidence that, contrary to umbilical cord blood and adult sources, stem cells present in both CD34(+) and CD34(-) FL populations can sustain long-term hematopoietic cultures. Furthermore, upon additional culture, CD34-depleted cell suspensions, devoid of SRCs, regenerated a population of CD34(+) cells possessing SRC function. Our studies suggest that compared to neonatal and adult sources, the phenotypical characteristics of putative human FL HSCs may be less strictly defined, and reinforce the accumulated evidence that human FL represents a unique, valuable alternative and highly proliferative source of HSCs for clinical applications.

Outside-in signaling through integrins and cadherins: a central mechanism to control epidermal growth and differentiation?

The process of epidermal renewal persists throughout the entire life of an organism. It begins when a keratinocyte progenitor leaves the stem cell compartment, undergoes a limited number of mitotic divisions, exits the cell cycle, and commits to terminal differentiation. At the end of this phase, the postmitotic keratinocytes detach from the basement membrane to build up the overlaying stratified epithelium. Although highly coordinated, this sequence of events is endowed with a remarkable versatility, which enables the quiescent keratinocyte to reintegrate into the cell cycle and become migratory when necessary, for example after wounding. It is this versatility that represents the Achilles heel of epithelial cells allowing for the development of severe pathologies. Over the past decade, compelling evidence has been provided that epithelial cancer cells achieve uncontrolled proliferation following hijacking of a "survival program" with PI3K/Akt and a "proliferation program" with growth factor receptor signaling at its core. Recent insights into adhesion receptor signaling now propose that integrins, but also cadherins, can centrally control these programs. It is suggested that the two types of adhesion receptors act as sensors to transmit extracellular stimuli in an outside-in mode, to inversely modulate epidermal growth factor receptor signaling and ensure cell survival. Hence, cell-matrix and cell-cell adhesion receptors likely play a more powerful and wide-ranging role than initially anticipated. This Perspective article discusses the relevance of this emerging field for epidermal growth and differentiation, which can be of importance for severe pathologies such as tumorigenesis and invasive metastasis, as well as psoriasis and Pemphigus vulgaris.