Experimentelle Therapieentwicklung für die akute lymphatische Leukämie

Bei Leukämie handelt es sich um eine Entartung von Vorläuferzellen der weißen Blutzellen (Leukozyten). Die hier betrachtete Form dieser Erkrankung ist die akute lymphatische Leukämie(ALL ), bei der vor allem Rückfallpatienten eine schlechte Diagnose haben. Demnach wird nach neuen Therapien gesucht, die neue Angriffspunkte für die Behandlung der ALL bieten. Die getestete Substanz 5-Azacytidin hat zwei therapeutische Wirkmechanismen. Zum einen das Hervorrufen des selbstinduzierte Zelltod (Apoptose) und zum anderen einen epigenetischen Effekt. Der epigenetische Effekt bewirkt eine Veränderung der Genregulation (Veränderung der Genaktivität) ohne die DNA - Sequenz zu beeinflussen. Dies kann mithilfe eines Screenings (Micoarraytechnologie) in behandelten und unbehandelten Proben verglichen werden. Da das Screening sehr global ist, erfolgt für eine Auswahl therapeutisch relevanter Gene eine Verifizierung mittels einer molekularbiologischen Methode (qRT -PCR ). Dabei wurden Gene mit erhöhter Aktivität bestätigt, MA EL; TM EM56; IL 1B; BCL 6; MS4A1 und FLT 3. Für jedes dieser Gene konnte ein positiver Nutzen für die Therapie einer ALL diskutiert werden. Für FLT 3 erfolgte sogar eine positive Kombination mit einer anderen therapeutischen Substanz. Der therapeutische Einsatz des 5-Azacytidins kann zukünftig eine wichtige Therapieoption für Patienten mit ALL darstellen

Material efficiency in companies of the manufacturing industry : Classification of measures

Part of: Seliger, Günther (Ed.): Innovative solutions : proceedings / 11th Global Conference on Sustainable Manufacturing, Berlin, Germany, 23rd - 25th September, 2013. - Berlin: Universitätsverlag der TU Berlin, 2013. - ISBN 978-3-7983-2609-5 (online). - http://nbn-resolving.de/urn:nbn:de:kobv:83-opus4-40276. - pp. 102–107.Improving material efficiency in the manufacturing industry is a sustainability imperative for companies due to economic and environmental advantages such as the reduction of material costs and resource use. Innovative solutions in terms of material efficiency measures are diverse and widespread. As a systematic assessment of efficiency approaches and their effects are likely to support dissemination and deployment, this paper aims to develop an approach that helps to classify material efficiency measures. The classification approach presents different dimensions and properties of material efficiency measures based on a literature analysis regarding existing classification approaches as well as on work that has been conducted for the Eco- Innovation Observatory. The classification has been designed as basis for an empirical impact assessment of material efficiency measures based on a data sample that stems from the German Material Efficiency Agency

Aetiopathogenesis and Phenomenology of Medically Unexplained Conditions

Functional somatic syndromes (FSS) are characterised by the presence of somatic symptoms and the absence of any demonstrable abnormalities of organ structure or function that would allow an attribution to a conventionally defined medical disease. There are numerous case definitions for different FSS, including chronic fatigue syndrome, fibromyalgia syndrome, or irritable bowel syndrome; however, to date, these do not have the status of nosological entities. The reason for this is that there is no universal consensus on how FSS should best be understood. The most extreme positions are those held by “lumpers”, who advocate the concept of one general FSS, and “splitters”, who are in favour of a concept that distinguishes between specific FSS (so-called “one versus many debate”). The overall aim of this thesis was to identify similarities and differences of FSS by studying aetiopathogenetic and phenomenological characteristics across a variety of syndromes. Concerning aetiopathogenesis, the role of stress was of particular interest. Based on the literature, a framework was postulated that illustrated the role of psychobiological stress in the development and maintenance of FSS. Specific parts of this framework were empirically tested and integrated. Concerning phenomenology, a number of syndromes was measured concomitantly to evaluate their overlaps, the role of depression and anxiety, and the latent structure of somatic symptoms. Different patient samples were recruited and a multi-methodological approach was adopted, including experimental, ambulatory assessment, and survey research designs. In sum, stress was confirmed as a factor that is involved in the predisposition, precipitation, and perpetuation of FSS in different patient samples; important mechanisms underlying this relationship were identified (studies I to III). Despite this commonality, syndrome overlap was rather low when the approach to case identification excluded clear-cut medical explanations for somatic symptoms (studies IV and V). This apparent discrepancy was reflected by the fact that symptoms pertaining to FSS could best be explained by a general and four symptom-specific factors (studies VI). Based on the findings of this thesis, the greatest confidence may be placed in stating that FSS are "one and many". It is conceivable that a high amount of stress during childhood or adulthood and subsequent alterations in stress-responsive systems as well as the cognitive style of somatoensory amplification represent endophentotypes that are common to medically unexplained conditions in general. The identified symptom-specific factors would then need to be understood as phenomenological variants of this process. Future attempts at classifying medically unexplained conditions should acknowledge both common and symptom-specific factors in order to foster prolific research

Structure of 3,4-Dihydroxy-2-butanone 4-Phosphate Synthase from Methanococcus jannaschii in Complex with Divalent Metal Ions and the Substrate Ribulose 5-Phosphate: implications for the catalytic mechanism

Skeletal rearrangements of carbohydrates are crucial for many biosynthetic pathways. In riboflavin biosynthesis ribulose 5-phosphate is converted into 3,4-dihydroxy-2-butanone 4-phosphate while its C4 atom is released as formate in a sequence of metal-dependent reactions. Here, we present the crystal structure of Methanococcus jannaschii 3,4-dihydroxy-2-butanone 4-phosphate synthase in complex with the substrate ribulose 5-phosphate at a dimetal center presumably consisting of non-catalytic zinc and calcium ions at 1.7-Å resolution. The carbonyl group (O2) and two out of three free hydroxyl groups (OH3 and OH4) of the substrate are metal-coordinated. We correlate previous mutational studies on this enzyme with the present structural results. Residues of the first coordination sphere involved in metal binding are indispensable for catalytic activity. Only Glu-185 of the second coordination sphere cannot be replaced without complete loss of activity. It contacts the C3 hydrogen atom directly and probably initiates enediol formation in concert with both metal ions to start the reaction sequence. Mechanistic similarities to Rubisco acting on the similar substrate ribulose 1,5-diphosphate in carbon dioxide fixation as well as other carbohydrate (reducto-) isomerases are discussed

On labour market discrimination against Roma in South East Europe

This paper directs interest on country-specific labour market discrimination Roma may suffer in South East Europe. The study lies in the tradition of statistical Blinder-Oaxaca decomposition analysis. We use microdata from UNDP's 2004 survey of Roma minorities, and apply a Bayesian approach, proposed by Keith and LeSage (2004), for the decomposition analysis of wage differentials. This approach is based on a robust Bayesian heteroscedastic linear regression model in conjunction with Markov Chain Monte Carlo (MCMC) estimation. The results obtained indicate the presence of labour market discrimination in Albania and Kosovo, but point to its absence in Bulgaria, Croatia, and Serbia

Why Does Psychotherapy Work and for Whom? Hormonal Answers

The questions of for whom and why psychotherapy is effective have been the focus of five decades of research. Most of this knowledge is based on self-report measures. Following the biopsychosocial model of mental disorders, this article explores the potential of hormones in answering these questions. The literature on cortisol, oxytocin, and oestradiol in psychotherapy was systematically searched, focusing on (a) baseline hormonal predictors of who may benefit from psychotherapy and (b) hormonal changes as indicators of therapeutic change. The search was limited to depression and anxiety disorders. In sum, the findings show that, of all three hormones, the role of cortisol is most established and that both cortisol and oxytocin are implicated in psychotherapy, although a causal role is still waiting to be demonstrated. Moreover, there is a differential role of hormones in the psychotherapy of depression versus anxiety. The directions of research mapped in this article may elucidate how psychotherapy can be selected to match patients’ endocrine states and how hormonal levels can be manipulated to improve outcomes

Soft-Feedback OMP for the Recovery of Discrete-Valued Sparse Signals

Publication in the conference proceedings of EUSIPCO, Nice, France, 201