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Search Results: 1 - 10 of 586 matches for " Dietmar Krex "
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Novel CIC Point Mutations and an Exon-Spanning, Homozygous Deletion Identified in Oligodendroglial Tumors by a Comprehensive Genomic Approach Including Transcriptome Sequencing
Sophie Eisenreich, Khalil Abou-El-Ardat, Karol Szafranski, Jaime A. Campos Valenzuela, Andreas Rump, Janice M. Nigro, Rolf Bjerkvig, Eva-Maria Gerlach, Karl Hackmann, Evelin Schr?ck, Dietmar Krex, Lars Kaderali, Gabriele Schackert, Matthias Platzer, Barbara Klink
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0076623
Abstract: Oligodendroglial tumors form a distinct subgroup of gliomas, characterized by a better response to treatment and prolonged overall survival. Most oligodendrogliomas and also some oligoastrocytomas are characterized by a unique and typical unbalanced translocation, der(1,19), resulting in a 1p/19q co-deletion. Candidate tumor suppressor genes targeted by these losses, CIC on 19q13.2 and FUBP1 on 1p31.1, were only recently discovered. We analyzed 17 oligodendrogliomas and oligoastrocytomas by applying a comprehensive approach consisting of RNA expression analysis, DNA sequencing of CIC, FUBP1, IDH1/2, and array CGH. We confirmed three different genetic subtypes in our samples: i) the “oligodendroglial” subtype with 1p/19q co-deletion in twelve out of 17 tumors; ii) the “astrocytic” subtype in three tumors; iii) the “other” subtype in two tumors. All twelve tumors with the 1p/19q co-deletion carried the most common IDH1 R132H mutation. In seven of these tumors, we found protein-disrupting point mutations in the remaining allele of CIC, four of which are novel. One of these tumors also had a deleterious mutation in FUBP1. Only by integrating RNA expression and array CGH data, were we able to discover an exon-spanning homozygous microdeletion within the remaining allele of CIC in an additional tumor with 1p/19q co-deletion. Therefore we propose that the mutation rate might be underestimated when looking at sequence variants alone. In conclusion, the high frequency and the spectrum of CIC mutations in our 1p/19q-codeleted tumor cohort support the hypothesis that CIC acts as a tumor suppressor in these tumors, whereas FUBP1 might play only a minor role.
Die Behandlung von lteren Patienten mit benignen oder malignen Hirntumoren
Krex D,Rudolph K,Schackert G
Journal für Neurologie, Neurochirurgie und Psychiatrie , 2011,
Abstract: Der demographische Wandel spiegelt sich zunehmend in unserem klinischen Alltag wider. Der Anteil an alten Patienten wird auch in der Neurochirurgie stetig gr er. Menschen jenseits des 65. Lebensjahres wurden bisher nur vereinzelt in klinischen Studien berücksichtigt, sodass die Datenlage zu evidenzbasierten Therapieempfehlungen dieser Altersgruppe entsprechend dürftig ist. Die vorliegende retrospektive Analyse besch ftigt sich mit der Frage, ob bei Patienten jenseits des 75. Lebensjahres mit einem Glioblastom oder einem Meningeom generell die gleiche operative und adjuvante Therapie angewendet werden sollte wie bei jüngeren Patienten, und ob h ufiger oder schwerwiegendere Komplikationen in dieser Altersgruppe auftreten. 105 Patienten mit Glioblastomen oder Meningeomen 75 Jahre wurden 97 Patienten mit gleichen Diagnosen und einem Alter 50 Jahre gegenübergestellt. Der Allgemein- und neurologische Zustand war bei den lteren initial schlechter als bei den Jüngeren. Die OP-assoziierten Komplikationen waren in beiden Gruppen gleich verteilt. Auff llig war jedoch ein erh hter Anteil an Patienten mit Antriebs- und Hirnleistungsst rungen in der Gruppe der 75-J hrigen, was zu einer vorübergehenden Pflegebedürftigkeit führte. Maligne Gliome wurden bei den lteren deutlich weniger adjuvant behandelt und das überleben war in dieser Gruppe signifikant schlechter. Daraus resultiert, dass auch alte Patienten mit malignen Gliomen oder Meningeomen in gleichem Ma e neurochirurgisch behandelt werden sollten wie jüngere Patienten. Auch sollte über eine intensivere adjuvante Therapie nachgedacht werden, um das überleben zu verbessern, was aber letztlich in klinischen Studien beurteilt werden muss, die auch diese Altersgruppe berücksichtigen.
Trust between Boundary-Spanning Agents: The Role of Relational Competencies  [PDF]
Isabella Hatak, Dietmar Roessl
Open Journal of Social Sciences (JSS) , 2015, DOI: 10.4236/jss.2015.33001

Against the background of principal-agent and transaction-cost theoretical considerations, this study addresses the question whether relational competencies relate to trust within cooperative relationships, taking into account also situational and personal factors. In its conclusion, the study presents an experimentally confirmed model (n = 282) that shows the strong causal relationship between relational competencies and trust allowing boundary-spanning agents to exert influence on the development and maintenance of complex cooperative relationships characterized by long-term objectives.

Combined Ang-2 and VEGF Targeting Therapies in Renal Cell Carcinoma  [PDF]
Nikolett Molnar, Dietmar W. Siemann
Journal of Cancer Therapy (JCT) , 2013, DOI: 10.4236/jct.2013.49A2001

Angiogenesis, the growth of new vessels from pre-existing ones, is an important feature of tumor growth that has been exploited as a therapeutic target in oncology. Given its key role in facilitating blood vessel sprouting, VEGF has been a major focus of anti-angiogenic strategies, but the observation of resistance in some clinical trials utilizing such agents has led to a search for new or complementary targets in angiogenesis process. The Angiopoietin/Tie2 pathway and in particular the Angiopoietin-2 (Ang-2) ligand which is critically involved in the destabilization of normal vasculature, has been identified as one such target. The current study investigated the potential benefits of combining an Ang-2 targeted therapy with small molecule VEGF targeted agents (Sunitinib, Cediranib) in a human renal cell carcinoma model. The results showed that while both Ang-2 and VEGF interference on their own impaired tumor growth and new blood vessel formation, the combination of agents that targeted both pathways resulted in significantly superior anti-tumor and anti-angiogenic effects.

Quantum Measurements Generating Structures of Numerical Events  [PDF]
Dietmar Dorninger, Helmut L?nger
Journal of Applied Mathematics and Physics (JAMP) , 2018, DOI: 10.4236/jamp.2018.65085
Abstract: Let S be a set of states of a physical system and p(s) the probability of an occurrence of an event when the system is in state s∈S. The function p from S to [0,1] is called a numerical event, multidimensional probability or, more precisely, S-probability. If a set of numerical events is ordered by the order of real functions one obtains a partial ordered set P in which the sum and difference of S-probabilities are related to their order within P. According to the structure that arises, this further opens up the opportunity to decide whether one deals with a quantum mechanical situation or a classical one. In this paper we focus on the situation that P is generated by a given set of measurements, i.e. S-probabilities, without assuming that these S-probabilities can be complemented by further measurements or are embeddable into Boolean algebras, assumptions that were made in most of the preceding papers. In particular, we study the generation by S-probabilities that can only assume the values 0 and 1, thus dealing with so called concrete logics. We characterize these logics under several suppositions that might occur with measurements and generalize our findings to arbitrary S-probabilities, this way providing a possibility to distinguish between potential classical and quantum situations and the fact that an obtained structure might not be sufficient for an appropriate decision. Moreover, we provide some explanatory examples from physics.
The development of drugs for treatment of sleeping sickness: a historical review
Dietmar Steverding
Parasites & Vectors , 2010, DOI: 10.1186/1756-3305-3-15
Abstract: Human African trypanosomiasis or sleeping sickness is a disease caused by two subspecies of Trypanosoma brucei, T. b. rhodesiense and T. b. gambiense. The parasites live and multiply extracellularly in blood and tissue fluids of their human host and are transmitted by the bite of infected tsetse flies (Glossina spp.). The occurrence of sleeping sickness is restricted to the distribution of tsetse flies which are exclusively found in sub-Saharan Africa between 14°N and 20°S [1]. More than 250 discrete active sleeping sickness foci in 36 African countries are recognised most of which are in rural areas [2].Trypanosoma b. rhodesiense is found in East and southern Africa whereas T. b. gambiense occurs in West and Central Africa. The course of sleeping sickness is different depending on the subspecies. Infections with T. b. rhodesiense lead to an acute form of the disease while infections with T. b. gambiense give rise to a chronic infection. The symptoms of the first stage of the disease, defined by the restriction of trypanosomes to the blood and lymph system, include fever, headache, joint pain and itching [3,4]. The clinical signs of the second stage of the disease, characterised by the invasion of trypanosomes into the central nervous system, are neurological and endocrinal disorders [3,4]. If left untreated, sleeping sickness patients infected with T. b. rhodesiense will die within months whereas those infected with T. b. gambiense usually survive for several years.In the late 19th Century, Africa experienced several sleeping sickness epidemics the most devastating of which was an epidemic with 300,000 to 500,000 deaths between 1896 and 1906 which mainly affected the Congo Basin and the Busoga focus in Uganda and Kenya [5]. The disastrous effect of this epidemic persuaded the various colonial administrations to call for their medical scientists to develop a cure for sleeping sickness. At that time, the field of chemotherapy was developing and had begun to make use
The history of African trypanosomiasis
Dietmar Steverding
Parasites & Vectors , 2008, DOI: 10.1186/1756-3305-1-3
Abstract: African trypanosomiasis is an infectious disease of humans and animals of similar aetiology and epidemiology. The causative agents of the disease are protozoan parasites of the genus Trypanosoma that live and multiply extracellularly in blood and tissue fluids of their mammalian hosts and are transmitted by the bite of infected tsetse flies (Glossina sp.). The distribution of trypanosomaisis in Africa corresponds to the range of tsetse flies and comprises currently an area of 8 million km2 between 14 degrees North and 20 degrees South latitude [1]. Throughout history, African trypanosomiasis has severely repressed the economic and cultural development of Central Africa.African animal trypanosomiasis or nagana disease is caused by T. congolense, T. vivax and T. brucei spp. In wild animals, these parasites cause relatively mild infections while in domestic animals they cause a severe, often fatal disease. All domestic animals can be affected by nagana and the symptoms are fever, listlessness, emaciation, hair loss, discharge from the eyes, oedema, anaemia, and paralysis. As the illness progresses the animals weaken more and more and eventually become unfit for work, hence the name of the disease "N'gana" which is a Zulu word that means "powerless/useless" [2]. Because of nagana, stock farming is very difficult within the tsetse belt.Human African trypanosomiasis or sleeping sickness is caused by two subspecies of T. brucei, T. brucei gambiense and T. brucei rhodesiense, while the third subspecies, T. brucei brucei, is only infectious to animals. T. b. gambiense is responsible for the chronic form of sleeping sickness in West and Central Africa, whereas T. b. rhodesiense gives rise to the acute form of the disease in East and Southern Africa. There are two distinct stages during the course of sleeping sickness. The first or early stage of the disease, also known as the haemolymphatic phase, is defined by the restriction of the trypanosomes to the blood and lymph system
From birdsong to speech: a plea for comparative approaches
Todt, Dietmar;
Anais da Academia Brasileira de Ciências , 2004, DOI: 10.1590/S0001-37652004000200003
Abstract: human language and speech are unique accomplishments. nevertheless, they share a number of characteristics with other systems of communication, and investigators have thus compared them to birdsong and the vocal signaling of nonhuman primates. particular interesting parallels concern the development of singing and speaking. these behaviors rely on auditory perception, subsequent memorization and finally, the generation of vocal imitations. several mechanisms help young individuals to deal with the various challenges during the time of signal development. specific differences aside, astounding parallels can be found also in how a human and a particularly accomplished bird like the common nightingale luscinia megarhynchos treat the experience of many different sound patterns or songs. as a consequence of such exposure, both human infants and young birds eventually acquire large repertoires of verbal or vocal signals. these achievements, however, require access to specific memory mechanisms which are well adapted to the purposes they serve, thereby allowing them to fulfil their species typical roles. with such aspects as a reference, birdsong is an excellent biological model for memory research and also an appropriate system for the study of evolutionary strategies in a very successful class of organisms.
Polysemy, polyvalence, and linking mismatches: the concept of RAIN and its codings in English, German, Italian, and Spanish
Zaefferer, Dietmar;
DELTA: Documenta??o de Estudos em Lingüística Teórica e Aplicada , 2002, DOI: 10.1590/S0102-44502002000300004
Abstract: based on an ontological frame for comparative onomasiological lexicology which embeds the rain eventity type as an exponent-shaped activity into a general linguistic ontology as well as an ontology of motion, the words for rain in two germanic and two romance languages are compared with respect to their semantic and syntactic variability. it turns out that the germanic forms are more flexible than the romance forms. english rain has the highest variability: it can be used with eight valencies, a nominal and seven verbal ones, and with five different meanings, and it is the only one to display a valence that combines an expletive subject with a cognate object as well as a causativized eventity meaning. on the other hand only german regnen has a resultativized meaning. the romance languages too show some internal variance: in allowing both an impersonal construction with a generalized meaning and a source construction, spanish llover is slightly more flexible than italian piovere. finally, an optimality theoretic account of the data is adumbrated in terms of three principles: avoid linking mismatches, avoid heterogeneity of sentence patterns, and avoid redundancy.
Pensamientos filosóficos sobre lo divino a partir de Friedrich Georg Jünger y Martin Heidegger
Teología y vida , 2009, DOI: 10.4067/S0049-34492009000200006
Abstract: both friedrich georg jünger and martin heidegger, in their considerations of the divine, highlight the figure of the daimonion. the present work brings to light certain central aspects of this convergence. in particular, it highlights the accent placed by both authors on the diamónica experience as transformation of the ordinary world and the decisive role of the poetic word in this experience.
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