MicroRNA expression profile in head and neck cancer: HOX-cluster embedded microRNA-196a and microRNA-10b dysregulation implicated in cell proliferation

Abstract Background Current evidence implicates aberrant microRNA expression patterns in human malignancies; measurement of microRNA expression may have diagnostic and prognostic applications. Roles for microRNAs in head and neck squamous cell carcinomas (HNSCC) are largely unknown. HNSCC, a smoking-related cancer, is one of the most common malignancies worldwide but reliable diagnostic and prognostic markers have not been discovered so far. Some studies have evaluated the potential use of microRNA as biomarkers with clinical application in HNSCC. Methods MicroRNA expression profile of oral squamous cell carcinoma samples was determined by means of DNA microarrays. We also performed gain-of-function assays for two differentially expressed microRNA using two squamous cell carcinoma cell lines and normal oral keratinocytes. The effect of the over-expression of these molecules was evaluated by means of global gene expression profiling and cell proliferation assessment. Results Altered microRNA expression was detected for a total of 72 microRNAs. Among these we found well studied molecules, such as the miR-17-92 cluster, comprising potent oncogenic microRNA, and miR-34, recently found to interact with p53. HOX-cluster embedded miR-196a/b and miR-10b were up- and down-regulated, respectively, in tumor samples. Since validated HOX gene targets for these microRNAs are not consistently deregulated in HNSCC, we performed gain-of-function experiments, in an attempt to outline their possible role. Our results suggest that both molecules interfere in cell proliferation through distinct processes, possibly targeting a small set of genes involved in cell cycle progression. Conclusions Functional data on miRNAs in HNSCC is still scarce. Our data corroborate current literature and brings new insights into the role of microRNAs in HNSCC. We also show that miR-196a and miR-10b, not previously associated with HNSCC, may play an oncogenic role in this disease through the deregulation of cell proliferation. The study of microRNA alterations in HNSCC is an essential step to the mechanistic understanding of tumor formation and could lead to the discovery of clinically relevant biomarkers.

Come città dell'infanzia. Architettura, educazione e immagine in due colonie per i figli degli Italiani all'estero a Cattolica e Tirrenia

The present doctoral dissertation deals with two significant case studies of Italian holiday camps which appear as interesting architectural experiences that reflect both the pedagogic and educational programmes of the fascist regime, and the discussion on the constructive and expressive principles that characterize the Italian architecture during the Thirties. The research explains the colony "XXVIII October for the sons of the Italian workers living abroad", today known as "Le Navi" ("The Ships"), built in Cattolica in 1934 and projected by the Roman architect Clemente Busiri Vici, and the feminine colony "for the sons of the Italian workers living abroad" built in 1934 in Tirrenia and projected by the architects Mario Paniconi and Giulio Pediconi. These holiday camps are the sole buildings commissioned directly by the Department in the Italian Foreign Office with the aim of offering a seaside stay to the sons of the Italians living in the colonies who, probably, could visit Italy only one time in their life. Firstly, the work illustrates the most relevant themes concerning these holiday camps, such as the representative intents that the buildings evoked to the children attending the places. Sun-bathing and group gymnastics were some of the rituals in the communal life, where order and discipline gave a precise internal organization to the spaces. Over the correspondence to practical functions, the figures and the forms of the different spaces of the buildings involve the children in an educational dimension. Subsequently, the function of the Department in the Italian Foreign Office and the planning and constructive ideas of the two colonies will be introduced. These colonies were conceived by a precise social project with educational, welfare and therapeutic aims. The elements, the spaces and the volumes create a fixed and theatrical scene of the life, full of ideological, political and celebratory overtones. Finally, the research shows that the relation between the architectural shape of the buildings and the rituals performed by fascist tutors produces an ideal space, extraneous to the external world that could influence the behavior of the children. The plan is to transmit to the children an image of Italy that will remain engraved in their minds once they have returned to their countries. In these projects there is the intent to transmit the image of "italianity" abroad. The way to do this was to plan for them a scenery which contains all the architectural elements of Italian cities. The holiday camps are proposed a sort of microcosm that appears as an "evocation" of the places and the spaces of Italian cities. The buildings appear as veritable "cities of childhood".

Enabling a direct path from end-user specifications to executable protocols in a biology laboratory environment

Biomedical analyses are becoming increasingly complex, with respect to both the type of the data to be produced and the procedures to be executed. This trend is expected to continue in the future. The development of information and protocol management systems that can sustain this challenge is therefore becoming an essential enabling factor for all actors in the field. The use of custom-built solutions that require the biology domain expert to acquire or procure software engineering expertise in the development of the laboratory infrastructure is not fully satisfactory because it incurs undesirable mutual knowledge dependencies between the two camps. We propose instead an infrastructure concept that enables the domain experts to express laboratory protocols using proper domain knowledge, free from the incidence and mediation of the software implementation artefacts. In the system that we propose this is made possible by basing the modelling language on an authoritative domain specific ontology and then using modern model-driven architecture technology to transform the user models in software artefacts ready for execution in a multi-agent based execution platform specialized for biomedical laboratories.

Transatlantic negotiations on "hell"?: W. E. B. Du Bois's visit to fascist Germany and Theodor W. Adorno's exile in the land of the culture industry

In 1936, the African-American intellectual W.E.B. Du Bois visited Nazi Germany for a period of five months. Two years later, the eleven-year-long American exile of the German philosopher Theodor W. Adorno began. From the latter’s perspective, the United States was the “home” of the Culture Industry. One intuitively assumes that these sojourns abroad must have amounted to “hell on earth” for both the civil rights activist W.E.B. Du Bois and the subtle intellectual Adorno. But was this really the case? Or did they perhaps arrive at totally different conclusions? This thesis deals with these questions and attempts to make sense of the experiences of both men. By way of a systematic and comparative analysis of published texts, hitherto unpublished documents and secondary literature, this dissertation first contextualizes Du Bois’s and Adorno’s transatlantic negotiations and then depicts them. The panoply of topics with which both men concerned themselves was diverse. In Du Bois’s case it encompassed Europe, science and technology, Wagner operas, the Olympics, industrial education, race relations, National Socialism and the German Africanist Diedrich Westermann. The opinion pieces which Du Bois wrote for the newspaper “Pittsburgh Courier” during his stay in Germany serve as a major source for this thesis. In his writings on America, Adorno concentrated on what he regarded as the universally victorious Enlightenment and the predominance of mass culture. This investigation also sheds light on the correspondences between the philosopher and Max Horkheimer, Thomas Mann, Walter Benjamin, Siegfried Kracauer and Oskar and Maria Wiesengrund. In these autobiographical texts, Adorno’s thoughts revolve around such diverse topics as the American landscape, his fears as German, Jew and Left-Hegelian as well as the loneliness of the refugee. This dissertation has to refute the intuitive assumption that Du Bois’s and Adorno’s experiences abroad were horrible events for them. Both men judged the foreign countries in which they were staying in an extremely differentiated and subtle manner. Du Bois, for example, was not racially discriminated against in Germany. He was also delighted by the country’s rich cultural offerings. Adorno, for his part, praised the U.S.’s humanity of everyday life and democratic spirit. In short: Although both men partly did have to deal with utterly negative experiences, the metaphor of “hell on earth” is simply untenable as an overall conclusion.

Das deutsche Kriegsgefangenenwesen 1939 - 1945

Zusammenfassung: Die vorliegende Untersuchung zum deutschen Kriegsgefangenenwesen (KGW) im Zweiten Weltkrieg schließt eine wichtige Lücke innerhalb der geschichtswissenschaftlichen Forschungen zum Themenkreis der Kriegsgefangenschaft in deutschem Gewahrsam. Bisherige Studien (bis einschließlich 1997) behandeln vor allem sozial- und kulturgeschichtliche Aspekte der Kriegsgefangenen (Kgf.), der Lagergesellschaft und dem Alltag von Soldaten in Kriegsgefangenschaft. Der Verfasser indes legt mit seiner Magisterarbeit erstmals eine Organisations- und Strukturgeschichte des deutschen Kriegsgefangenenwesens von 1939 bis 1945 vor, welche fundamentale Grundlagen der deutschen militärischen Lagerorganisation und Verwaltung dokumentiert. So wird die Entwicklung von den Vorkriegsplanungen bis zum Kriegsende anhand der zentralen Dienststellen herausgearbeitet und im Kontext des Genfer Kriegsgefangenenabkommens von 1929 und völkerrechtlicher Implikationen gewichtet. Hiermit untrennbar verbundene Einflußnahmen nichtmilitärischer Stellen in die Entscheidungsgewalt der Streitkräfte im Heimatkriegsgebiet und in den Wehrmachtbefehlshaberbereichen werden nicht zuletzt auch anhand mehrerer Organigramme veranschaulicht. Zudem dokumentiert und analysiert die Untersuchung die im Kriegsverlauf stetig verschärften Maßnahmen zur Fluchtprävention und der konzertierten Fahndung nach geflohenen Kriegsgefangenen: Die Machterosion des Oberkommandos der Wehrmacht (OKW) zugunsten des Reichsführers-SS, des Reichssicherheitshauptamts und nicht zuletzt der Parteikanzlei der NSDAP wird so augenfällig. Trotz eminenter Schriftgutverluste kann der Verfasser vor allem anhand einer nahezu vollständig erhaltenen Schlüsselquelle die Stellenbesetzung und Organisationsstruktur der mit Kriegsgefangenenfragen befassten Stellen im OKW rekonstruieren. Die Auswertung dieser Sammelmitteilungen / Befehlssammlung für das Kriegsgefangenenwesen sowie an anderer Stelle überlieferter Organisationsbefehle ermöglicht wichtige Änderungen am derzeitigen Forschungsstand. Darüber hinaus beschäftigt sich die vorliegende Untersuchung mit dem Arbeitseinsatz Kriegsgefangener in der deutschen Wirtschaft als in der zweiten Kriegshälfte zentralem Element der Kriegsgefangenschaft. Außerdem wird beleuchtet, welche politischen, (rassen)ideologischen oder reziprok konnotierten Faktoren den Stellenwert gefangener Soldaten unterschiedlicher Nationalität innerhalb der Gefangenenhierarchie im deutschen Kriegsgefangenenwesen bestimmten. Inhalt: 1. Einführung; 2. Die Entwicklung des Kriegsvölkerrechts und das Genfer Kriegsgefangenenabkommen von 1929; 3. Einleitende Bemerkungen zum deutschen Kriegsgefangenenwesen: Quellenlage, Grundlagen; 4. Organisationsstruktur und Aufgaben des KGW: Zuständigkeiten für Kgf. in OKW und OKH, Abt. Wehrmachtverluste und Kriegsgefangene, der General z.b.V. für das KGW 1939 bis Ende 1941, Allgemeine und Organisationsabteilung seit Januar 1942, Generalinspekteur und Inspekteur des KGW von Juli 1943 bis Oktober 1944, das Kriegsgefangenenwesen unter Himmler seit Oktober 1944; 5. Die Kriegsgefangenenlager: Lagertypen, Anzahl und Verwendung, die Gesamtzahl Kgf. und Belegstärken ausgewählter Lager; 6. Richtlinien für KGL: Die Sammelmitteilungen / Befehlssammlung für das KGW, Lagerorganisation und Behandlung Kriegsgefangener; 7. Die Post der Kriegsgefangenen: Tätigkeit von Auslandsbriefprüfstelle, Abwehr III Referat Kgf. und Abwehrstellen der Wehrkreise, Vorgaben für Postüberwachung und Stimmungsberichte der Asten, Befehle zur Kgf-Post und Kooperation mit Hilfsorganisationen und Schutzmächten; 8. Fluchtprävention: Bestimmungen und Maßnahmen zur Fluchtvereitelung, der Fluchterlass vom 22.09.1942, der Sonderfahndungsplan der Sicherheitspolizei und des SD vom 28.09.1942, Erlass zur Kriegsfahndung vom 5.12.1942, der Fluchterlaß vom 02.07.1943, der Erlaß zur Mitarbeit NSDAP bei Groß- und Kriegsfahndungen vom 10.07.1943, Schulung zur Fluchtprävention auf Wehrkreisebene 1944, Preisausschreiben "Wie verhindere ich Fluchten?" vom 09.04.1945, Anwerbung von V-Leuten durch die Abwehr; 9. Arbeitseinsatz Kriegsgefangener in der deutschen Wirtschaft und beteiligte Stellen; 10. Der Status Kriegsgefangener unterschiedlicher Nationalitäten im Vergleich; 11. Schluss

Eine Million Algerier lernen im 20. Jahrhundert zu leben. Umsiedlungslager und Zwangsmodernisierung im Algerienkrieg 1954–1962

Als eines der erstaunlichsten Merkmale des algerisch-französischen Unabhängigkeitskriegs 1954-1962 darf die Kombination von militärischer Aufstandsbekämpfung und zivilen Reformprojekten gelten. Diese Verschränkung lässt sich an keinem Aspekt dieses Krieges so deutlich beobachten wie an der französischen Umsiedlungspolitik. Bis zu drei Millionen Menschen wurden während des Krieges von der französischen Armee gewaltsam aus ihren Dörfern vertreiben und in eigens angelegte Sammellager, die «camps de regroupement», umgesiedelt. Was als rein militärische Maßnahme begann, entwickelte sich schnell zu einem gewaltigen ländlichen Entwicklungsprogramm. Durch das Versprechen einer umfassenden Modernisierung aller Lebensbereiche im Schnellverfahren sollten die Insassen der Lager zu loyalen Anhängern des Projekts eines französischen Algeriens gemacht werden. Die «camps de regroupement» lassen sich als Modernisierungslaboratorien beschreiben, in denen sich scheinbar widersprüchliche Elemente wie Entwicklungshilfe mit äußerst rigider Bevölkerungskontrolle und totalitär anmutenden Maßnahmen des social engineering zu einem einzigartigen Ensemble verbanden. [ABSTRACT FROM AUTHOR]

The co-evolution of development needs and IOR forms: development by committee in Bosnia

This work highlights opportunities and obstacles to success in four task forces typically found at different times in states of conflict, transition, and development. They include: refugee return, media issues, privatization of state-owned enterprises, and efforts to promote business development. Based on over 180 in-depth interviews and observations of dozens of meetings during five lengthy field research trips to the Bosnian region between 1999 and 2005, this manuscript analyzes how these four task forces differed in terms of context, strategy, organization, and management in an attempt to understand the co-evolution of international development needs and the interorganizational forms that address them.

Trends in Migrations of Refugees in Serbia

This project aimed to establish a comprehensive long-term projection of refugee migration trends in Serbia which would allow the different organisations engaged in caring for refugees to plan their work more effectively. Mr. Cvetkovic studied first the official records of numbers and origins of refugees and the various definitions used to describe refugees, exiled persons, etc., considering also the indication of nationality, i.e. Serb or Yugoslav, and the future intentions expressed by refugees. He concluded that more than three quarters of the total number of refugees in Serbia wish to remain in Serbia/Federal Republic of Yugoslavia, and only 20% wish to repatriate. He concludes that the situation in relation to the ethnic-national structure of Serbia is extremely complicated, even to the point of chaos. One certainty is that sooner or later a huge majority of the refugees in Serbia today will be granted full citizenship and will then participate in the choice of the political system and the dominant national values and institutions of the country. The experiences of the refugees, as well as of their fellow nationals in Serbia, make it relatively unlikely that they will make rational choices that could produce a balance between civil democracy and national totalitarianism. Insofar as overall political relations within Serbia and its Federation with Montenegro develop along democratic lines, the civic identity of Serbs (as opposed to their national/ethnic status) can be expected to become stronger, and the civil and national to become an integral part of thinking which does not represent a challenge to the democratic state. This would help ensure that the migratory movements of the Serbs and of other national and ethnic groups in the region are motivated by economic rather than political or ethnic reasons.

Panel 7: Survival Strategies

Panel 7: Survival Strategies Moriya Rachmani, Ben-Gurion University, Israel: “Rituals in Concentration and Extermination Camps and Near Death Situations: Existence, Order, Identity” Download paper (login required) Barbara Hutzelmann, Ludwig-Maximilians University, Germany: “‘I Didn’t Want to Die.’ Jewish Children’s Strategies of Survival in Slovakia: Chances and Limitations" Download paper (login required) Liviu Carare, The Romanian Academy “George Bariţiu” Institute of History, Cluj-Napoca, Romania: "Jews of Czernowitz (1941-1942): Murder, Ghettoization and Deportation" Download paper (login required) Chair: Alexis Herr and Adara Goldberg, Clark UniversityComment: Johannes Lang, Danish Institute for International Studies, Copenhagen

Analgesic activity of a non-peptide imidazolidinedione somatostatin agonist: in vitro and in vivo studies in rat

Several lines of evidence support an important role for somatostatin receptors (SSTRs) in pain modulation. The therapeutic use of established SSTR peptide agonists for this indication is limited by their broad range of effects, need for intrathecal delivery, and short half-life. Therefore, the goal of the present study was to investigate the analgesic effect of SCR007, a new, highly selective SSTR2 non-peptide agonist. Behavioral studies demonstrated that paw withdrawal latencies to heat were significantly increased following intraplantar SCR007. Furthermore, both intraperitoneal and intraplantar injection of SCR007 significantly reduced formalin- and capsaicin-induced flinching and lifting/licking nociceptive behaviors. Recordings from nociceptors using an in vitro glabrous skin-nerve preparation showed that SCR007 reduced heat responses in a dose-dependent fashion, bradykinin-induced excitation, heat sensitization and capsaicin-induced excitation. In both the behavioral and single fiber studies, the SCR007 effects were reversed by the SSTR antagonist cyclo-somatostatin, demonstrating receptor specificity. In the single fiber studies, the opioid antagonist naloxone did not reverse SCR007-induced anti-nociception suggesting that SCR007 did not exert its effects through activation of opioid receptors. Analysis of cAMP/protein kinase A (PKA) involvement demonstrated that SCR007 prevented forskolin- and Sp-8-Br-cAMPS (a PKA activator)-induced heat sensitization, supporting the hypothesis that SCR007-induced inhibition could involve a down-regulation of the cAMP/PKA pathway. These data provide several lines of evidence that the non-peptide imidazolidinedione SSTR2 agonist SCR007 is a promising anti-nociceptive and analgesic agent for the treatment of pain of peripheral and/or central origin.

High incidence of optic disc swelling at very high altitudes

OBJECTIVES: To determine the incidence of optic disc swelling as a possible indicator of cerebral edema in a large group of healthy mountaineers exposed to very high altitudes and to correlate these findings with various clinical and environmental factors and occurrence of acute mountain sickness and high-altitude cerebral edema. METHODS: This multidisciplinary, prospective, observational cohort study was performed in 2005 within the scope of a medical research expedition to Muztagh Ata (7546 m [24,751 ft]) in Western Xinjiang Province, China. Twenty-seven healthy mountaineers aged 26 to 62 years participated. Medical examinations were performed in Switzerland 1 month before and 4 1/2 months after the expedition. Ophthalmologic examinations were performed at 4 high camps (maximum elevation, 6865 m [22,517 ft]). Optic disc status was documented using digital photography. Further assessments included arterial oxygen saturation and cerebral acute mountain sickness scores. RESULTS: Sixteen of 27 study subjects (59%) exhibited optic disc swelling during their stay at high altitudes, with complete regression on return to lowlands. Significant correlation was noted between optic disc swelling and lower arterial oxygen saturation (odds ratio, 0.86 per percentage of arterial oxygen saturation; 95% confidence interval, 0.81-0.92; P < .001), younger age (odds ratio, 0.95 per year; 95% confidence interval, 0.90-0.99; P = .03), and higher cerebral acute mountain sickness scores (odds ratio, 2.32 per 0.1 point; 95% confidence interval, 1.48-3.63; P < .001). CONCLUSION: Optic disc swelling occurs frequently in high-altitude climbers and is correlated with peripheral oxygen saturation and symptoms of acute mountain sickness. It is most likely the result of hypoxia-induced brain volume increase.