Prediction of outcome in patients with low-grade squamous intraepithelial lesions by fluorescence in situ hybridization analysis of human papillomavirus, TERC, and MYC

BACKGROUND Cytology is an excellent method with which to diagnose preinvasive lesions of the uterine cervix, but it suffers from limited specificity for clinically significant lesions. Supplementary methods might predict the natural course of the detected lesions. The objective of the current study was to test whether a multicolor fluorescence in situ hybridization (FISH) assay might help to stratify abnormal results of Papanicolaou tests. METHODS A total of 219 liquid-based cytology specimens of low-grade squamous intraepithelial lesions (LSIL), 49 atypical squamous cells of undetermined significance (ASCUS) specimens, 52 high-grade squamous intraepithelial lesion (HSIL) specimens, and 50 normal samples were assessed by FISH with probes for the human papillomavirus (HPV), MYC, and telomerase RNA component (TERC). Subtyping of HPV by polymerase chain reaction (PCR) was performed in a subset of cases (n=206). RESULTS There was a significant correlation found between HPV detection by FISH and PCR (P<.0001). In patients with LSILs, the presence of HPV detected by FISH was significantly associated with disease progression (P<.0001). An increased MYC and/or TERC gene copy number (>2 signals in>10% of cells) prevailed in 43% of ASCUS specimens and was more frequent in HSIL (85%) than in LSIL (33%) (HSIL vs LSIL: P<.0001). Increased TERC gene copy number was significantly correlated with progression of LSIL (P<.01; odds ratio, 7.44; area under the receiver operating characteristic curve, 0.73; positive predictive value, 0.30; negative predictive value, 0.94) CONCLUSIONS: The detection of HPV by FISH analysis is feasible in liquid-based cytology and is significantly correlated with HPV analysis by PCR. The analysis of TERC gene copy number may be useful for risk stratification in patients with LSIL.

Floods at the northern foothills of the Tatra Mountains — A Polish-Swiss research project

The present paper introduces the topical area of the Polish-Swiss research project FLORIST (Flood risk on the northern foothills of the Tatra Mountains), informs on its objectives, and reports on initial results. The Tatra Mountains are the area of the highest precipitation in Poland and largely contribute to flood generation. The project is focused around four competence clusters: observation-based climatology, model-based climate change projections and impact assessment, dendrogeomorphology, and impact of large wood debris on fluvial processes. The knowledge generated in the FLORIST project is likely to have impact on understanding and interpretation of flood risk on the northern foothills of the Tatra Mountains, in the past, present, and future. It can help solving important practical problems related to flood risk reduction strategies and flood preparedness.

Printed Narrative: The Festival Books for Archduke Ernest of Austria from Brussels and Antwerp 1594

Workshop „The Narrative in Eastern and Western Art“, Graduate School of Letters, Kyoto, 2-5 December 2013 Abstract by Ivo Raband, University of Berne Printed Narrative: The Festival Books for Ernest of Austria from Brussels and Antwerp 1594 During the early modern period the medium of the festival book became increasingly more important as an object of ‘political narration’ throughout Europe. Focusing on Netherlandish examples from the sixteenth and seventeenth centuries, my talk will focus on the festival books printed for the Joyous Entries of Archduke Ernest of Austria (1553–1595). Ernest was appointed Governor General of the Netherlands by King Philipp II in 1593, being the first Habsburg Prince to reside in Brussels since 30 years. In Brussels and Antwerp, the Archduke was greeted with the traditional Blijde Imkomst, Joyous Entry, which dates back to the fourteenth century and was a necessity to actually become the sovereign of Brabant and Antwerp and to uphold the privileges of the cities. Decorated with ephemeral triumphal arches, stages, and tableaux vivants, both cities welcomed Ernest and, at the same time, demonstrated their civic self-assurance and negotiated their statuses. In honor of these events of civic power, the city magistrates commissioned festival books. These books combine a Latin text with a description of the events and the ephemeral structures, including circa 30 engravings and etchings. Being the only visual manifestation of the Joyous Entries, the books became important representational objects. The prints featured in festival books will be my point of departure for discussing the importance of narrative political prints and the concept of the early modern festival book as a ‘political object’. By comparing the prints from Ernest’s entries with others from the period between 1549 and 1635, I will show how the prints became as important as the event itself. Thus, I want to pose the question of whether it would have been possible to substitute a printed version of the event for the actual ceremony.

The Gas6-Axl Interaction Mediates Endothelial Uptake of Platelet Microparticles.

Upon activation, platelets release plasma-membrane derived microparticles (PMPs) exposing phosphatidylserine (PS) on their surface. The function and clearance mechanism of these MPs are incompletely understood. As they are pro-coagulant and potentially pro-inflammatory, rapid clearance from the circulation is essential for prevention of thrombotic diseases. The tyrosine kinase receptors Tyro3, Axl and Mer (TAMs) and their ligands protein S and Gas6 are involved in the uptake of PS-exposing apoptotic cells in macrophages and dendritic cells. Both TAMs and their ligands are expressed in the vasculature, the functional significance of which is poorly understood. In this study we investigated how vascular TAMs and their ligands may mediate endothelial uptake of PMPs. PMPs, generated from purified human platelets, were isolated by ultracentrifugation and labeled with biotin or PKH67. The uptake of labeled MPs in the presence of protein S and Gas6 in human aortic endothelial cells (HAEC) and human umbilical vein endothelial cells (HUVEC) was monitored by flow cytometry, western blotting and confocal/electron microscopy. We found that both endothelial cell types can phagocytose PMPs, and using TAM-blocking antibodies or siRNA knock-down of individual TAMs we show that the uptake is mediated by endothelial Axl and Gas6. As circulating PMPs-levels were not altered in Gas6-/- mice compared to Gas6+/+ mice, we hypothesize that the Gas6-mediated uptake is not a means to clear the bulk of circulating PMPs but may serve to phagocytose PMPs locally generated at sites of platelet activation and as a way to affect endothelial responses.