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Oncogenic rearrangements leading to targetable gene fusions are well-established cancer driver events in lung adenocarcinoma. Accurate and reliable detection of these gene fusions is crucial to select the appropriate targeted therapy for each patient. We compared the targeted next-generation-sequencing Oncomine Focus Assay (OFA; Thermo Fisher Scientific) with conventional ALK FISH and anti-Alk immunohistochemistry in a cohort of 52 lung adenocarcinomas (10 ALK rearranged, 18 non-ALK rearranged, and 24 untested cases). We found a sensitivity and specificity of 100% for detection of ALK rearrangements using the OFA panel. In addition, targeted next generation sequencing allowed us to analyze a set of 23 driver genes in a single assay. Besides EML4-ALK (11/52 cases), we detected EZR-ROS1 (1/52 cases), KIF5B-RET (1/52 cases) and MET-MET (4/52 cases) fusions. All EML4-ALK, EZR-ROS1 and KIF5B-RET fusions were confirmed by multiplexed targeted next generation sequencing assay (Oncomine Solid Tumor Fusion Transcript Kit, Thermo Fisher Scientific). All cases with EML4-ALK rearrangement were confirmed by Alk immunohistochemistry and all but one by ALK FISH. In our experience, targeted next-generation sequencing is a reliable and timesaving tool for multiplexed detection of targetable rearrangements. Therefore, targeted next-generation sequencing represents an efficient alternative to time-consuming single target assays currently used in molecular pathology.
The p300/CBP‐associated factor (PCAF) and related GCN5 bromodomain‐containing lysine acetyl transferases are members of subfamily I of the bromodomain phylogenetic tree. Iterative cycles of rational inhibitor design and biophysical characterization led to the discovery of the triazolopthalazine‐based L‐45 (dubbed L‐Moses) as the first potent, selective, and cell‐active PCAF bromodomain (Brd) inhibitor. Synthesis from readily available (1R,2S)‐(−)‐norephedrine furnished L‐45 in enantiopure form. L‐45 was shown to disrupt PCAF‐Brd histone H3.3 interaction in cells using a nanoBRET assay, and a co‐crystal structure of L‐45 with the homologous Brd PfGCN5 from Plasmodium falciparum rationalizes the high selectivity for PCAF and GCN5 bromodomains. Compound L‐45 shows no observable cytotoxicity in peripheral blood mononuclear cells (PBMC), good cell‐permeability, and metabolic stability in human and mouse liver microsomes, supporting its potential for in vivo use.
Objective. Traumatic injury or severe surgery leads to a profound immune response with a diminished functionality of monocytes and subsequently their IL-1β release. IL-1β plays an important role in host immunity and protection against infections. Its biological activation via IL-1β-precursor processing requires the transcription of inflammasome components and their activation. Deregulated activity of NOD-like receptor inflammasomes (NLR) like NLRP3 that leads to the maturation of IL-1β has been described in various diseases. While the role of other inflammasomes has been studied in monocytes, nothing is known about NLRP3 inflammasome after a traumatic injury. Here, the role of the NLRP3 inflammasome in impaired monocyte functionality after a traumatic injury was analyzed.
Measurements and Main Results. Ex vivo-in vitro stimulation of isolated CD14+ monocytes with lipopolysaccharide (LPS) showed a significantly higher IL-1β secretion in healthy volunteers (HV) compared to trauma patients (TP) after admission. Reduced IL-1β secretion was paralleled by significantly lowered gene expression of NLRP3 in monocytes from TP compared to those of HV. Transfection of monocytes with NLRP3-encoding plasmid recovered the functionality of monocytes from TP regarding the IL-1β secretion.
Conclusions. This study demonstrates that CD14+ monocytes from TP are significantly diminished in their function and that the presence of NLRP3 components is necessary in recovering the ability of monocytes to produce active IL-1β. This recovery of the NLRP3 inflammasome in monocytes may imply a new target for treatment and therapy of immune suppression after severe injury.
Species identification of adult African blowflies (Diptera: Calliphoridae) of forensic importance
(2017)
Necrophagous blowflies can provide an excellent source of evidence for forensic entomologists and are also relevant to problems in public health, medicine, and animal health. However, access to useful information about these blowflies is constrained by the need to correctly identify the flies, and the poor availability of reliable, accessible identification tools is a serious obstacle to the development of forensic entomology in the majority of African countries. In response to this need, a high-quality key to the adults of all species of forensically relevant blowflies of Africa has been prepared, drawing on high-quality entomological materials and modern focus-stacking photomicroscopy. This new key can be easily applied by investigators inexperienced in the taxonomy of blowflies and is made available through a highly accessible online platform. Problematic diagnostic characters used in previous keys are discussed.
2010 yılında Polonya'nın Varşova kentinde "Vielheit und Einheit der Germanistik" teması ile gerçekleştirilen 12. Uluslararası Germanistik Kongresi’nin ardından 13. Uluslararası Germanistik Kongresi 2015 yılında "Germanistik zwischen Tradition und Innovation" teması ile Çin Halk Cumhuriyeti Şanghay Tongji Üniversitesi'nde 23-30 Ağustos 2015 tarihlerinde düzenlendi. Türkiye'nin de aralarında bulunduğu 96 ülkeden kongreye katılan 1200'ün üzerinde değerli akademisyen ve araştırmacı kongrede bildirilerini sundular.
Der 13. Weltkongress der Internationalen Vereinigung für Germanistik (IVG) fand vom 23.08.2015 bis zum 30.08.2015 unter dem Motto "Germanistik zwischen Tradition und Innovation" in Shanghai/China statt. Gastgeber dieses vielfältigen und reichhaltigen internationalen Kongresses war die Tongji-Universität. Mehr als 1200 Teilnehmerinnen und Teilnehmer aus 69 Ländern haben an diesem Kongress, der alle fünf Jahre organisiert wird, teilgenommen. Auch die Türkei beteiligte sich mit ca. 30 Wissenschaftlerinnen und Wissenschaftlern aus Edirne bis Van an diesem Kongress.
Das wissenschaftliche Interesse auf dem Feld der Germanistik ist in den letzten Jahren in Rumänien, auch dank Herta Müller, die 2009 den Nobelpreis für Literatur bekommen hat, stark gestiegen. Nach dem letzten Kongress der Germanisten Rumäniens 2012 in Bukarest wurde der 10. Kongress der Germanisten Rumäniens vom 01. bis 04. Juni 2015 in der Aula an der Universität Transilvania in Braşov/Kronstadt veranstaltet. Die Tagung wird alle drei Jahre an jeweils wechselnden Hochschulen vom dortigen Germanistik-Fachbereich veranstaltet, was zeigt, dass die Germanistik in Rumänien an vielen Orten durch zum Teil kleine, aber aktive Lehrstühle vertreten ist.
Considering the misunderstanding of the particles used as an adverb by itself in closely related languages, we will try to provide the comprehension of sense of language about this area, which is missing in German. For this purpose, opposite language pairs seeming logical and etimological proofs about language variation will be presented. Firstly, we will try to explain what the sense of language is. We believe that it is more appropriate to say 'language acquisition' which can be acquired and developed by means of activities in foreign language classes. Examples verify this. In the conclusion, some other clarifying questions follow.
Sowohl international als auch national ist erkennbar, dass Länder in Bereichen Wirtschaft, kommunikative und informative Technologien, Politik, Bildung und Gesellschaft in unterschiedlicher Art und Weise mit kulturellen bzw. interkulturellen Tendenzen konfrontiert sind. Diese Tatsachen reflektieren somit, dass Gesellschaften immer mehr mit interkulturellen Herausforderungen in Kontakt kommen. Interkulturelles Lernen, Interkulturalität und interkulturelle Kompetenz enthalten gleichfalls im gegenwärtigen und modernen Fremdsprachenunterricht eine bedeutende Rolle und ein wichtiges Aufgabenfeld.
Present conditions are affecting the educational process and as a result of these changes restructuring these processes is essential. There is no doubt that in teaching foreign languages in general and in particular German as a foreign language, one of the prerequisites to gain for providing a qualified German language teaching is the training of qualified and well equipped German teachers. In this context one of the substantial competences in the training process is the linguistic competence. It is aimed that at the end of their study period, German language teacher candidates should have the ability of using the German language in written and spoken area and creating models for their prospective students.
Despite the new technological developments writing has not lost its importance; on the contrary, ist importance has been increasing day by day. German teacher candidates should be trained to be able to express themself written as well as verbally to respond to their students' writing needs. For this reason students who graduated from the German Language Teaching Department of Hasan Ali Yücel Faculty of Education of Istanbul University in 2013-2014 academic year were asked to evaluate their writing competence.
The self assessments results of the candidate teachers are going to be compared with the results of the writing competence part of the Goethe Zertifikat C1 examination. The aim is to determine proficiency in the duration of 4 years. The results also constitute the scientific basis of curricular discussions in the field of writing courses of the German Language Teaching Department.