116 research outputs found
Therapie des Magenkarzinoms im Wandel der Zeit (1881 - 2000)
Operative und adjuvante Therapieverfahren des Magenkarzinoms werden ĂŒber einen Zeitraum von 120 Jahren aufgezeigt. Die Gastrektomie hat die distale Magenresektion in den 40-iger Jahren abgelöst. OperationsmortalitĂ€t und 5-Jahres-Ăberlebensrate haben bei beiden Verfahren drastisch abgenommen. Multimodale Therapiekonzepte gewinnen in den letzten Jahrzehnten an Bedeutung. FĂŒr die adjuvante Chemotherapie liegen kaum erfolgsversprechende Studien vor. Durch die neoadjuvante Chemotherapie ist ein Anstieg an R0-Resektionen zu erzielen. Randomisierte Studien bezĂŒglich eines Ăberlebensvorteils durch neoadjuvante Chemotherapie und intraoperative Radiotherapie stehen noch aus. Die systematisch erweiterte Lymphknotendissektion hat eine zunehmende Akzeptanz gefunden. AbschlieĂend werden Ergebnisse vorgestellt, die auf der Auswertung der KrankenblĂ€tter von 115 Patienten, die in der Klinik fĂŒr Allgemeine Chirurgie der UniversitĂ€t MĂŒnster wegen eines Magenkarzinoms behandelt wurden, beruhen
Common and divergent features in transcriptional control of the homologous small RNAs GlmY and GlmZ in Enterobacteriaceae
Small RNAs GlmY and GlmZ compose a cascade that feedback-regulates synthesis of enzyme GlmS in Enterobacteriaceae. Here, we analyzed the transcriptional regulation of glmY/glmZ from Yersinia pseudotuberculosis, Salmonella typhimurium and Escherichia coli, as representatives for other enterobacterial species, which exhibit similar promoter architectures. The GlmY and GlmZ sRNAs of Y. pseudotuberculosis are transcribed from Ï54-promoters that require activation by the response regulator GlrR through binding to three conserved sites located upstream of the promoters. This also applies to glmY/glmZ of S. typhimurium and glmY of E. coli, but as a difference additional Ï70-promoters overlap the Ï54-promoters and initiate transcription at the same site. In contrast, E. coli glmZ is transcribed from a single Ï70-promoter. Thus, transcription of glmY and glmZ is controlled by Ï54 and the two-component system GlrR/GlrK (QseF/QseE) in Y. pseudotuberculosis and presumably in many other Enterobacteria. However, in a subset of species such as E. coli this relationship is partially lost in favor of Ï70-dependent transcription. In addition, we show that activity of the Ï54-promoter of E. coli glmY requires binding of the integration host factor to sites upstream of the promoter. Finally, evidence is provided that phosphorylation of GlrR increases its activity and thereby sRNA expression
Cell-based non-invasive prenatal testing for monogenic disorders:confirmation of unaffected fetuses following preimplantation genetic testing
PURPOSE: Proof of concept of the use of cell-based non-invasive prenatal testing (cbNIPT) as an alternative to chorionic villus sampling (CVS) following preimplantation genetic testing for monogenic disorders (PGT-M). METHOD: PGT-M was performed by combined testing of short tandem repeat (STR) markers and direct mutation detection, followed by transfer of an unaffected embryo. Patients who opted for follow-up of PGT-M by CVS had blood sampled, from which potential fetal extravillous throphoblast cells were isolated. The cell origin and mutational status were determined by combined testing of STR markers and direct mutation detection using the same setup as during PGT. The cbNIPT results with respect to the mutational status were compared to those of genetic testing of the CVS. RESULTS: Eight patients had blood collected between gestational weeks 10 and 13, from which 33 potential fetal cell samples were isolated. Twenty-seven out of 33 isolated cell samples were successfully tested (82%), of which 24 were of fetal origin (89%). This corresponds to a median of 2.5 successfully tested fetal cell samples per case (range 1â6). All fetal cell samples had a genetic profile identical to that of the transferred embryo confirming a pregnancy with an unaffected fetus, in accordance with the CVS results. CONCLUSION: These findings show that although measures are needed to enhance the test success rate and the number of cells identified, cbNIPT is a promising alternative to CVS. TRIAL REGISTRATION NUMBER: N-20180001 SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10815-021-02104-5
New basal cell carcinoma susceptibility loci.
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This article is open access.In an ongoing screen for DNA sequence variants that confer risk of cutaneous basal cell carcinoma (BCC), we conduct a genome-wide association study (GWAS) of 24,988,228 SNPs and small indels detected through whole-genome sequencing of 2,636 Icelanders and imputed into 4,572 BCC patients and 266,358 controls. Here we show the discovery of four new BCC susceptibility loci: 2p24 MYCN (rs57244888[C], OR=0.76, P=4.7 Ă 10(-12)), 2q33 CASP8-ALS2CR12 (rs13014235[C], OR=1.15, P=1.5 Ă 10(-9)), 8q21 ZFHX4 (rs28727938[G], OR=0.70, P=3.5 Ă 10(-12)) and 10p14 GATA3 (rs73635312[A], OR=0.74, P=2.4 Ă 10(-16)). Fine mapping reveals that two variants correlated with rs73635312[A] occur in conserved binding sites for the GATA3 transcription factor. In addition, expression microarrays and RNA-seq show that rs13014235[C] and a related SNP rs700635[C] are associated with expression of CASP8 splice variants in which sequences from intron 8 are retained.NCI\SAIC-Frederick, Inc. (SAIC-F) 10XS170
Roswell Park Cancer Institute 10XS171
Science Care Inc. X10S172
Laboratory, Data Analysis and Coordinating Center (LDACC)
HHSN268201000029C
SAIC-F
10ST1035
HHSN261200800001E
Brain Bank
DA006227
DA033684
N01MH000028
University of Geneva
MH090941
MH101814
University of Chicago
MH090951
MH090937
MH101820
MH101825
University of North Carolina-Chapel Hill
MH090936
MH101819
Harvard University
MH090948
Stanford University
MH101782
Washington University St Louis
MH101810
University of Pennsylvania
MH10182
An intercomparison study of four different techniques for measuring the chemical composition of nanoparticles
Currently, the complete chemical characterization of nanoparticles (<â100ânm) represents an analytical challenge, since these particles are abundant in number but have negligible mass. Several methods for particle-phase characterization have been recently developed to better detect and infer more accurately the sources and fates of sub-100ânm particles, but a detailed comparison of different approaches is missing. Here we report on the chemical composition of secondary organic aerosol (SOA) nanoparticles from experimental studies of α-pinene ozonolysis at â50, â30, and â10ââC and intercompare the results measured by different techniques. The experiments were performed at the Cosmics Leaving OUtdoor Droplets (CLOUD) chamber at the European Organization for Nuclear Research (CERN). The chemical composition was measured simultaneously by four different techniques: (1) thermal desorptionâdifferential mobility analyzer (TDâDMA) coupled to a NO chemical ionizationâatmospheric-pressure-interfaceâtime-of-flight (CIâAPiâTOF) mass spectrometer, (2) filter inlet for gases and aerosols (FIGAERO) coupled to an I high-resolution time-of-flight chemical ionization mass spectrometer (HRToF-CIMS), (3) extractive electrospray Na ionization time-of-flight mass spectrometer (EESI-TOF), and (4) offline analysis of filters (FILTER) using ultra-high-performance liquid chromatography (UHPLC) and heated electrospray ionization (HESI) coupled to an Orbitrap high-resolution mass spectrometer (HRMS). Intercomparison was performed by contrasting the observed chemical composition as a function of oxidation state and carbon number, by estimating the volatility and comparing the fraction of volatility classes, and by comparing the thermal desorption behavior (for the thermal desorption techniques: TDâDMA and FIGAERO) and performing positive matrix factorization (PMF) analysis for the thermograms. We found that the methods generally agree on the most important compounds that are found in the nanoparticles. However, they do see different parts of the organic spectrum. We suggest potential explanations for these differences: thermal decomposition, aging, sampling artifacts, etc. We applied PMF analysis and found insights of thermal decomposition in the TDâDMA and the FIGAERO
Hidden politics of power and governmentality in transitional justice and peacebuilding:The problem of âbringing the local back inâ
This paper examines âthe localâ in peacebuilding by examining how âlocalâ transitional justice projects can become spaces of power inequalities. The paper argues that focusing on how âthe localâ contests or interacts with âthe internationalâ in peacebuilding and post-conflict contexts obscures contestations and power relations amongst different local actors, and how inequalities and power asymmetries can be entrenched and reproduced through internationally funded local projects. The paper argues that externally funded projects aimed at emancipating âlocalsâ entrench inequalities and create local elites that become complicit in governing the conduct and participation of other less empowered âlocalsâ. The paper thus proposes that specific local actorsâoften those in charge of externally funded peacebuilding projectsâshould also be conceptualised as governing agents: able to discipline and regulate other local actorsâ voices and their agency, and thus (re)construct ideas about what âthe localâ is, or is not
Synergistic HNOâHSOâNH upper tropospheric particle formation
New particle formation in the upper free troposphere is a major global source of cloud condensation nuclei (CCN). However, the precursor vapours that drive the process are not well understood. With experiments performed under upper tropospheric conditions in the CERN CLOUD chamber, we show that nitric acid, sulfuric acid and ammonia form particles synergistically, at rates that are orders of magnitude faster than those from any two of the three components. The importance of this mechanism depends on the availability of ammonia, which was previously thought to be efficiently scavenged by cloud droplets during convection. However, surprisingly high concentrations of ammonia and ammonium nitrate have recently been observed in the upper troposphere over the Asian monsoon region5,6. Once particles have formed, co-condensation of ammonia and abundant nitric acid alone is sufficient to drive rapid growth to CCN sizes with only trace sulfate. Moreover, our measurements show that these CCN are also highly efficient ice nucleating particlesâcomparable to desert dust. Our model simulations confirm that ammonia is efficiently convected aloft during the Asian monsoon, driving rapid, multi-acid HNOâHSOâNH nucleation in the upper troposphere and producing ice nucleating particles that spread across the mid-latitude Northern Hemisphere
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