Deep molecular response is reached by the majority of patients treated with imatinib, predicts survival, and is achieved more quickly by optimized high-dose imatinib: results from the randomized CML-study IV

PURPOSE Deep molecular response (MR(4.5)) defines a subgroup of patients with chronic myeloid leukemia (CML) who may stay in unmaintained remission after treatment discontinuation. It is unclear how many patients achieve MR(4.5) under different treatment modalities and whether MR(4.5) predicts survival. PATIENTS AND METHODS Patients from the randomized CML-Study IV were analyzed for confirmed MR(4.5) which was defined as ≥ 4.5 log reduction of BCR-ABL on the international scale (IS) and determined by reverse transcriptase polymerase chain reaction in two consecutive analyses. Landmark analyses were performed to assess the impact of MR(4.5) on survival. RESULTS Of 1,551 randomly assigned patients, 1,524 were assessable. After a median observation time of 67.5 months, 5-year overall survival (OS) was 90%, 5-year progression-free-survival was 87.5%, and 8-year OS was 86%. The cumulative incidence of MR(4.5) after 9 years was 70% (median, 4.9 years); confirmed MR(4.5) was 54%. MR(4.5) was reached more quickly with optimized high-dose imatinib than with imatinib 400 mg/day (P = .016). Independent of treatment approach, confirmed MR(4.5) at 4 years predicted significantly higher survival probabilities than 0.1% to 1% IS, which corresponds to complete cytogenetic remission (8-year OS, 92% v 83%; P = .047). High-dose imatinib and early major molecular remission predicted MR(4.5). No patient with confirmed MR(4.5) has experienced progression. CONCLUSION MR(4.5) is a new molecular predictor of long-term outcome, is reached by a majority of patients treated with imatinib, and is achieved more quickly with optimized high-dose imatinib, which may provide an improved therapeutic basis for treatment discontinuation in CML.

Na 1 Nachlass Max Horkheimer, 657 - "The Philosophy of Western Society", "Bericht über die Aktivitäten des Instituts für Sozialforschung für Robert M. MacIver", "Über die Tätigkeit des Instituts für Sozialforschung", "Stipendiaten des Instituts für Sozialforschung: Forschungsberichte", "Research Projects of the International Institut of Social Research" (p. IX 56-IX 59.2)

Über das Forschungsprogramm: The Philosophy of Western Society. Teilstück des allgemeinen Forschungsprogramms, veröffentlicht unter dem Untertitel: "The Philosophy of Social Science", in: "International Institute of Social Research. A Report of Its History, Aims and Activites, 1933-1938", New York (1938?), S. 19, Typoskript mit eigenhändiger Korrektur, 2 Blatt; Bericht über die Aktivitäten des Instituts für Sozialforschung für Robert M. MacIver, 1938-39: 1. Bericht vom 7.12.1939; a) Typoskript, englisch, 9 Blatt; b) Typoskript, als Brief von Pollock an Robert M. MacIver, Typoskript 10 Blatt; c) Entwurf Typoskript, englisch, 15 Blatt; d) Entwurf Typoskript, deutsch, 17 Blatt; MacIver, Robert M.: 1 Brief mit Unterschrift an Friedrich Pollock, New York, 27.04.1938, 1 Blatt; "Some data on the Institut`s Staff and Activities", 11.03.1938, zwei Typoskripte, je 2 Blatt; Über die Tätigkeiten des Instituts für Sozialforschung. Verschiedene Berichte. 1939; Aufstellung der Forschungsgebiete verschiedener Mitarbeiter des Instituts. Ohne Datum, Typoskript, 9 Blatt; Aufstellung der Forschungsgebiete verschiedener Mitarbeiter des Institutes, aus einem Bericht. Typoskript, 7 Blatt; Bericht an den Präsidenten des Columbia University. Typoskript, 2 Blatt; "Contribution of Dr. Franz Neumann to the Round Table Discussion, Chicago, Social Science Reaserach Building" Dezember 1939; a) Typoskript mit Handschriftlichen Korrekturen, 3 Blatt; b) Typoskript, 3 Blatt; "Statment on the objectives of the International Institut of Social Research". Typoskript, 2 Blatt; Stipendiaten des Instituts für Sozialforschung: Forschungsberichte, Ende 1939; Adorno, Theodor W.: a) Typoskript, englisch, mit eigenhändigen Korrekturen, 4 Blatt; b) Typoskript, deutsch, 3 Blatt; Beck, Maximilian: "Geschichte des Begriffs der Vernunft von Platon bis Husserl (Outline)". Typoskript, englisch und deutsch, mit handschriftlichen Korrekturen, 7 Blatt; Flechtheim, Ossip K.: Typoskript mit handschriftlichen Ergänzungen, 1 Blatt; Fried, Hans Ernest: Typoskript, 1 Blatt, 16.11.1939; Grossmann, Henryk: "Capitalism in the 13th Century"; a) Typoskript, englisch, mit handschriftlichen Korrekturen, 6 Blatt; b) Typoskript, englisch, 6 Blatt; c) Typoskript, deutsch, 4 Blatt; Grossmann, Henryk: "The Classical Theory and Marxism"; a) Typoskript, englisch, mit handschriftlichen Korrekturen, 2 Blatt; b) Typoskript, deutsch, mit handschriftlichen Korrekturen, 2 Blatt; Kirchheimer, Otto: Manuskript, 1 Blatt; Lauterbach, Albert: a) Typoskript, englisch, mit handschriftlichen Korrekturen, 2 Blatt; b) Typoskript, deutsch, mit handschriftlichen Korrekturen, 1 Blatt; Marcuse, Herbert: Typoskript mit handschriftlichen Korrekturen, 2 Blatt; Neumann, Franz L.: Typoskript, 2 Blatt; Wittfogel, Karl August: Typsokript, 2 Blatt; Zilsel, Edgar: Typoskript, 4 Blatt; Research Projects of the International Institute of Social Research. nicht vor 1939; Beschreibung der Forschungsprojekte: Pollock, Friedrich: "Economic and Social Cosequences of a Prepardness Economy". Neumann, Franz L.: "The Rule of Law". Fromm, Erich: "The German Worker in the Weiman Republic". Kirchheimer,Otto: "Criminal Law and Social Structure". Marcuse, Herbert: " A Text and Source Book for the History of Philosophy". Fromm, Erich: "Character Structure of Modern Man". Neumann, Franz L.: "The Theory and Practice of European Labor Law". Wittfogel, Karl August; Wittfogel-Lang, Olga: "The Chinese Family"; Dasselbe wie in "Beschreibung der Forschungsprojekte", ausgenommen Pollock, Friedrich: "Economic and Social Cosquences of a Prepardness Economy" und Fromm, Erich: "The German Worker in the Weimar Republic", zusätzlich Kirchner, Otto; Weil, Felix: "Changes in Social Stratification, National Income, and Living Standards of Germany since 1933"; 1 Ordner, Typoskript mit eigenhändigen Korrekturen, 49 Blatt;

Core physics and safety analysis of Generation-IV Sodium Fast Reactors using existing and newly developed computational tools

El futuro de la energía nuclear de fisión dependerá, entre otros factores, de la capacidad que las nuevas tecnologías demuestren para solventar los principales retos a largo plazo que se plantean. Los principales retos se pueden resumir en los siguientes aspectos: la capacidad de proporcionar una solución final, segura y fiable a los residuos radiactivos; así como dar solución a la limitación de recursos naturales necesarios para alimentar los reactores nucleares; y por último, una mejora robusta en la seguridad de las centrales que en definitiva evite cualquier daño potencial tanto en la población como en el medio ambiente como consecuencia de cualquier escenario imaginable o más allá de lo imaginable. Siguiendo estas motivaciones, la Generación IV de reactores nucleares surge con el compromiso de proporcionar electricidad de forma sostenible, segura, económica y evitando la proliferación de material fisible. Entre los sistemas conceptuales que se consideran para la Gen IV, los reactores rápidos destacan por su capacidad potencial de transmutar actínidos a la vez que permiten una utilización óptima de los recursos naturales. Entre los refrigerantes que se plantean, el sodio parece una de las soluciones más prometedoras. Como consecuencia, esta tesis surgió dentro del marco del proyecto europeo CP-ESFR con el principal objetivo de evaluar la física de núcleo y seguridad de los reactores rápidos refrigerados por sodio, al tiempo que se desarrollaron herramientas apropiadas para dichos análisis. Efectivamente, en una primera parte de la tesis, se abarca el estudio de la física del núcleo de un reactor rápido representativo, incluyendo el análisis detallado de la capacidad de transmutar actínidos minoritarios. Como resultado de dichos análisis, se publicó un artículo en la revista Annals of Nuclear Energy [96]. Por otra parte, a través de un análisis de un hipotético escenario nuclear español, se evalúo la disponibilidad de recursos naturales necesarios en el caso particular de España para alimentar una flota específica de reactores rápidos, siguiendo varios escenarios de demanda, y teniendo en cuenta la capacidad de reproducción de plutonio que tienen estos sistemas. Como resultado de este trabajo también surgió una publicación en otra revista científica de prestigio internacional como es Energy Conversion and Management [97]. Con objeto de realizar esos y otros análisis, se desarrollaron diversos modelos del núcleo del ESFR siguiendo varias configuraciones, y para diferentes códigos. Por otro lado, con objeto de poder realizar análisis de seguridad de reactores rápidos, son necesarias herramientas multidimensionales de alta fidelidad específicas para reactores rápidos. Dichas herramientas deben integrar fenómenos relacionados con la neutrónica y con la termo-hidráulica, entre otros, mediante una aproximación multi-física. Siguiendo este objetivo, se evalúo el código de difusión neutrónica ANDES para su aplicación a reactores rápidos. ANDES es un código de resolución nodal que se encuentra implementado dentro del sistema COBAYA3 y está basado en el método ACMFD. Por lo tanto, el método ACMFD fue sometido a una revisión en profundidad para evaluar su aptitud para la aplicación a reactores rápidos. Durante ese proceso, se identificaron determinadas limitaciones que se discutirán a lo largo de este trabajo, junto con los desarrollos que se han elaborado e implementado para la resolución de dichas dificultades. Por otra parte, se desarrolló satisfactoriamente el acomplamiento del código neutrónico ANDES con un código termo-hidráulico de subcanales llamado SUBCHANFLOW, desarrollado recientemente en el KIT. Como conclusión de esta parte, todos los desarrollos implementados son evaluados y verificados. En paralelo con esos desarrollos, se calcularon para el núcleo del ESFR las secciones eficaces en multigrupos homogeneizadas a nivel nodal, así como otros parámetros neutrónicos, mediante los códigos ERANOS, primero, y SERPENT, después. Dichos parámetros se utilizaron más adelante para realizar cálculos estacionarios con ANDES. Además, como consecuencia de la contribución de la UPM al paquete de seguridad del proyecto CP-ESFR, se calcularon mediante el código SERPENT los parámetros de cinética puntual que se necesitan introducir en los típicos códigos termo-hidráulicos de planta, para estudios de seguridad. En concreto, dichos parámetros sirvieron para el análisis del impacto que tienen los actínidos minoritarios en el comportamiento de transitorios. Concluyendo, la tesis presenta una aproximación sistemática y multidisciplinar aplicada al análisis de seguridad y comportamiento neutrónico de los reactores rápidos de sodio de la Gen-IV, usando herramientas de cálculo existentes y recién desarrolladas ad' hoc para tal aplicación. Se ha empleado una cantidad importante de tiempo en identificar limitaciones de los métodos nodales analíticos en su aplicación en multigrupos a reactores rápidos, y se proponen interesantes soluciones para abordarlas. ABSTRACT The future of nuclear reactors will depend, among other aspects, on the capability to solve the long-term challenges linked to this technology. These are the capability to provide a definite, safe and reliable solution to the nuclear wastes; the limitation of natural resources, needed to fuel the reactors; and last but not least, the improved safety, which would avoid any potential damage on the public and or environment as a consequence of any imaginable and beyond imaginable circumstance. Following these motivations, the IV Generation of nuclear reactors arises, with the aim to provide sustainable, safe, economic and proliferationresistant electricity. Among the systems considered for the Gen IV, fast reactors have a representative role thanks to their potential capacity to transmute actinides together with the optimal usage of natural resources, being the sodium fast reactors the most promising concept. As a consequence, this thesis was born in the framework of the CP-ESFR project with the generic aim of evaluating the core physics and safety of sodium fast reactors, as well as the development of the approppriated tools to perform such analyses. Indeed, in a first part of this thesis work, the main core physics of the representative sodium fast reactor are assessed, including a detailed analysis of the capability to transmute minor actinides. A part of the results obtained have been published in Annals of Nuclear Energy [96]. Moreover, by means of the analysis of a hypothetical Spanish nuclear scenario, the availability of natural resources required to deploy an specific fleet of fast reactor is assessed, taking into account the breeding properties of such systems. This work also led to a publication in Energy Conversion and Management [97]. In order to perform those and other analyses, several models of the ESFR core were created for different codes. On the other hand, in order to perform safety studies of sodium fast reactors, high fidelity multidimensional analysis tools for sodium fast reactors are required. Such tools should integrate neutronic and thermal-hydraulic phenomena in a multi-physics approach. Following this motivation, the neutron diffusion code ANDES is assessed for sodium fast reactor applications. ANDES is the nodal solver implemented inside the multigroup pin-by-pin diffusion COBAYA3 code, and is based on the analytical method ACMFD. Thus, the ACMFD was verified for SFR applications and while doing so, some limitations were encountered, which are discussed through this work. In order to solve those, some new developments are proposed and implemented in ANDES. Moreover, the code was satisfactorily coupled with the thermal-hydraulic code SUBCHANFLOW, recently developed at KIT. Finally, the different implementations are verified. In addition to those developments, the node homogenized multigroup cross sections and other neutron parameters were obtained for the ESFR core using ERANOS and SERPENT codes, and employed afterwards by ANDES to perform steady state calculations. Moreover, as a result of the UPM contribution to the safety package of the CP-ESFR project, the point kinetic parameters required by the typical plant thermal-hydraulic codes were computed for the ESFR core using SERPENT, which final aim was the assessment of the impact of minor actinides in transient behaviour. All in all, the thesis provides a systematic and multi-purpose approach applied to the assessment of safety and performance parameters of Generation-IV SFR, using existing and newly developed analytical tools. An important amount of time was employed in identifying the limitations that the analytical nodal diffusion methods present when applied to fast reactors following a multigroup approach, and interesting solutions are proposed in order to overcome them.

Suppression of an absolute defect in Type IV pilus biogenesis by loss-of-function mutations in pilT, a twitching motility gene in Neisseria gonorrhoeae

Type IV pili of Neisseria gonorrhoeae, the Gram-negative etiologic agent of gonorrhea, facilitate colonization of the human host. Gonococcal PilT, a protein belonging to a large family of molecules sharing a highly conserved nucleotide binding domain motif, has been shown to be dispensable for organelle biogenesis but essential for twitching motility and competence for genetic transformation. Here, we show that the defect in pilus biogenesis resulting from mutations in the pilC gene, encoding a putative pilus-associated adhesin for human tissue, can be suppressed by the absence of functional PilT. These data conclusively demonstrate that PilT influences the Type IV pilus biogenesis pathway and strongly suggest that organelle expression is a dynamic process. In addition, these findings imply that PilT antagonizes the process of organelle biogenesis and provide the basis for a model for how the counteractive roles of PilT and PilC might relate mechanistically to the phenomenon of twitching motility.

Germany on Russia. Yes to links, no to rapprochement. OSW Point of View Number 39, March 2014

The German media have been correctly describing the atmosphere between the Chancellor's Office and the Kremlin as the chilliest in years. Various factors have laid bare the fact that the strategic partnership between Germany and Russia is at best currently undergoing a 'technical pause’: the underwhelming outcomes of the German-Russian intergovernmental consultations in the autumn of 2012 and of Chancellor Merkel's meeting with President Putin during the Hanover fair in the spring of 2013, as well as the way in which the EU dealt with the Cyprus debt issue and, finally, the support that Germany has extended to the anti-presidential protests in Ukraine. Meanwhile, the priorities of Germany's foreign and economic policy have changed considerably, not only as a result of the eurozone crisis, but also, even more importantly, because the attention of German business and politics has been shifting to the so-called neue Gestaltungsmächte, or new regional powers. German politicians increasingly believe that Russia should not be offered new methods or mechanisms of co-operation. Firstly, because the existing ones have not been fully utilised, and secondly, because Germany at this stage seems to have no idea of what the long-term strategy of co-operation with Putin's Russia should be.

The Dilemmas of Diffusion: Institutional Transfer & the Remaking of Vocational Training Practices in Eastern Germany, CES Germany & Europe Working Papers, No. 05.10, 1996

Through a case study of the diffusion of the celebrated West Gennan "dual system" of vocational training to the territory of the fonner German Democratic Republic, we develop the argument that local sociopolitical relations matter crucially for the successful transfer and implementation of institutional arrangements. Notwithstanding massive levels of government funding, the presence of complementary supports, and the concerted efforts of Ger­many's social partners, the dual system is experiencing significant difficulties in the new federal states of the East. These difficulties are not due simply to the particular politics of unification (the wholesale transfer of West German institutions whether or not they were appropriate to Eastern Germany) nor even simply to the paucity of dynamic private firms capable of and willing to train new apprentices. The difficulties stem also from the under­ lying weaknesses of the East German sociopolitical infrastructure on which the entire dual system rests. This. hy­ pothesis is elaborated and substantiated through a range of data on training in the East and especially through the use of detailed case studies of Leipzig and Chemrutz.

On the accession of Charles Emanuel the IVth to the throne = In occasione dell' avvenimento al trono dell' augustissimo sovrano Carlo Emmanuele IV.

Verses in English signed: Frances Negri Gobbet. Italian translation signed: Aretofilo Dianeo (?--print unclear)

Memoirs of the Emperor Jahangueir /

Mode of access: Internet.

The reform act, 1832; the correspondence of the late Earl Grey with His Majesty King William IV. and with Sir Herbert Taylor, from Nov. 1830 to June 1832;

Mode of access: Internet.

The Elector's guide. Addressed to the freeholders of the county of York.

No. I. The "Catholic question".--No. II. The general state of the country banks and paper money; Death of Alexander, emperor of Russia; State of parties in the kingdom; A letter to Fountayne Wilson, esq.; Duncombe and the treadmill; Poetry and miscellanies.--No. III. A letter to the Duke of York; Auri sacra fames; or, Sturdy beggars: a county job; Church Methodism; A Protestant confessor; His Majesty's speech to Parliament; Miscellanies, and poetry.--No. IV. A letter to Daniel Sykes, esq. on West Indian slavery; Catholic and Protestant; The last man; Confidence in banks; Hints to electors; The proceedings in Parliament, &c., &c., &c.--No. V. An address to the suffering people of England; Slavery; A letter to Sir John Bayley, knt,; Banks; The Protestant champion; Poetry, &c., &c.--No. VI. A charge of His Grace the Archbishop of York to the clergy of the diocese; A secret; A good action.--No. VII. Observations upon county representation; A full account of the county meeting, &c., &c.

Ioannis Cantacuzeni eximperatoris Historiarum libri IV : graece et latine /

Covers mostly the years 1320-1356.

Memoirs of Mrs. Fitzherbert; with an account of her marriage with H. R. H. the Prince of Wales, afterwards King George IV.

Mode of access: Internet.

Briefwechsel zwischen König Johann von Sachsen und den Königen Friedrich Wilhelm IV. und Wilhelm I. von Preussen,

Mode of access: Internet.

A narrative of events connected with the first abdication of the Emperor Napoleon, his embarkation at Frejus and voyage to Elba, on board His Majesty's ship Undaunted.

Mode of access: Internet.