Vor der Revolution

Dieses Open-Access-Buch setzt sich zum Ziel, eingebettet in historische Kontexte paralleler Kalter Kriege im globalen und regionalen Rahmen die historische Genese der amerikanisch-iranischen Sonderbeziehungen nach dem Zweiten Weltkrieg und deren Transformation in den drei anschließenden Jahrzehnten zu analysieren. In der Geschichte der Staatenwelt nach dem Zweiten Weltkrieg gibt es wohl kaum ein bilaterales Verhältnis, das eine ähnlich tiefgreifende Kehrtwende von engsten, zwischenzeitlich fast „besonderen“ Beziehungen hin zu gegenseitiger Dämonisierung und unüberwindlich erscheinender Feindschaft erfahren hat, wie dasjenige zwischen den Vereinigten Staaten von Amerika und Iran. Zentraler Bezugspunkt sind dabei die Entscheidungen und die strukturellen Zwänge, die zur engen Anlehnung der amerikanischen Politik an den Hof und die Person des Schahs führten, was die Entfremdung der oppositionellen Kräfte und die Entstehung des Feindbildes USA während der Revolutionsphase zur Folge hatte. Der Autor Roland Popp ist Politischer Berater/Analyst, wohnhaft in Zürich/Schweiz. Seine Themenschwerpunkte sind der gegenwärtige Nahe und Mittlere Osten und Fragen der internationalen Sicherheitspolitik. Er berät Unternehmen bezüglich politischer Risiken und ist häufiger Gast und Interviewpartner im Schweizer Fernsehen

Laser Spectroscopic Technique for Direct Identification of a Single Virus I: FASTER CARS

From the famous 1918 H1N1 influenza to the present COVID-19 pandemic, the need for improved virial detection techniques is all too apparent. The aim of the present paper is to show that identification of individual virus particles in clinical sample materials quickly and reliably is near at hand. First of all, our team has developed techniques for identification of virions based on a modular atomic force microscopy (AFM). Furthermore, Femtosecond Adaptive Spectroscopic Techniques with Enhanced Resolution via Coherent Anti-Stokes Raman Scattering (FASTER CARS) [1] using tip-enhanced techniques markedly improves the sensitivity.Comment: 16 pages, 3 figure

Laser spectroscopic technique for direct identification of a single virus I: FASTER CARS

From the famous 1918 H1N1 influenza to the present COVID-19 pandemic, the need for improved viral detection techniques is all too apparent. The aim of the present paper is to show that identification of individual virus particles in clinical sample materials quickly and reliably is near at hand. First of all, our team has developed techniques for identification of virions based on a modular atomic force microscopy (AFM). Furthermore, femtosecond adaptive spectroscopic techniques with enhanced resolution via coherent anti-Stokes Raman scattering (FASTER CARS) using tip-enhanced techniques markedly improves the sensitivity [M. O. Scully, et al, Proc. Natl. Acad. Sci. U.S.A. 99, 10994-11001 (2002)]

Phase chaos in the anisotropic complex Ginzburg-Landau Equation

Of the various interesting solutions found in the two-dimensional complex Ginzburg-Landau equation for anisotropic systems, the phase-chaotic states show particularly novel features. They exist in a broader parameter range than in the isotropic case, and often even broader than in one dimension. They typically represent the global attractor of the system. There exist two variants of phase chaos: a quasi-one dimensional and a two-dimensional solution. The transition to defect chaos is of intermittent type.Comment: 4 pages RevTeX, 5 figures, little changes in figures and references, typos removed, accepted as Rapid Commun. in Phys. Rev.

Three-Dimensional Maps of All Chromosomes in Human Male Fibroblast Nuclei and Prometaphase Rosettes

Studies of higher-order chromatin arrangements are an essential part of ongoing attempts to explore changes in epigenome structure and their functional implications during development and cell differentiation. However, the extent and cell-type-specificity of three-dimensional (3D) chromosome arrangements has remained controversial. In order to overcome technical limitations of previous studies, we have developed tools that allow the quantitative 3D positional mapping of all chromosomes simultaneously. We present unequivocal evidence for a probabilistic 3D order of prometaphase chromosomes, as well as of chromosome territories (CTs) in nuclei of quiescent (G0) and cycling (early S-phase) human diploid fibroblasts (46, XY). Radial distance measurements showed a probabilistic, highly nonrandom correlation with chromosome size: small chromosomes—independently of their gene density—were distributed significantly closer to the center of the nucleus or prometaphase rosette, while large chromosomes were located closer to the nuclear or rosette rim. This arrangement was independently confirmed in both human fibroblast and amniotic fluid cell nuclei. Notably, these cell types exhibit flat-ellipsoidal cell nuclei, in contrast to the spherical nuclei of lymphocytes and several other human cell types, for which we and others previously demonstrated gene-density-correlated radial 3D CT arrangements. Modeling of 3D CT arrangements suggests that cell-type-specific differences in radial CT arrangements are not solely due to geometrical constraints that result from nuclear shape differences. We also found gene-density-correlated arrangements of higher-order chromatin shared by all human cell types studied so far. Chromatin domains, which are gene-poor, form a layer beneath the nuclear envelope, while gene-dense chromatin is enriched in the nuclear interior. We discuss the possible functional implications of this finding

Activation of the PI3K/AKT Pathway in Merkel Cell Carcinoma

Merkel cell carcinoma (MCC) is a highly aggressive skin cancer with an increasing incidence. The understanding of the molecular carcinogenesis of MCC is limited. Here, we scrutinized the PI3K/AKT pathway, one of the major pathways activated in human cancer, in MCC. Immunohistochemical analysis of 41 tumor tissues and 9 MCC cell lines revealed high levels of AKT phosphorylation at threonine 308 in 88% of samples. Notably, the AKT phosphorylation was not correlated with the presence or absence of the Merkel cell polyoma virus (MCV). Accordingly, knock-down of the large and small T antigen by shRNA in MCV positive MCC cells did not affect phosphorylation of AKT. We also analyzed 46 MCC samples for activating PIK3CA and AKT1 mutations. Oncogenic PIK3CA mutations were found in 2/46 (4%) MCCs whereas mutations in exon 4 of AKT1 were absent. MCC cell lines demonstrated a high sensitivity towards the PI3K inhibitor LY-294002. This finding together with our observation that the PI3K/AKT pathway is activated in the majority of human MCCs identifies PI3K/AKT as a potential new therapeutic target for MCC patients

Metastatic disease to the pancreas and spleen

Isolated metastases to the pancreas and spleen are a rare occurrence. When they are diagnosed, pancreatic metastases are most often from renal cell carcinoma, lung cancer, and breast cancer. The most common source of splenic metastases is gynecological in origin; the overwhelming majority is ovarian. If extensive staging studies reveal these metastases to be isolated, then curative resection may be warranted. This review will demonstrate that long-term survival may be achieved in patients with isolated metastases and a prolonged disease-free interval

The many possible climates from the Paris Agreement’s aim of 1.5 °C warming

The United Nations’ Paris Agreement includes the aim of pursuing efforts to limit global warming to only 1.5 °C above pre-industrial levels. However, it is not clear what the resulting climate would look like across the globe and over time. Here we show that trajectories towards a ‘1.5 °C warmer world’ may result in vastly different outcomes at regional scales, owing to variations in the pace and location of climate change and their interactions with society’s mitigation, adaptation and vulnerabilities to climate change. Pursuing policies that are considered to be consistent with the 1.5 °C aim will not completely remove the risk of global temperatures being much higher or of some regional extremes reaching dangerous levels for ecosystems and societies over the coming decades

Differential Gene Expression Patterns of EBV Infected EBNA-3A Positive and Negative Human B Lymphocytes

The genome of Epstein-Barr virus (EBV) encodes 86 proteins, but only a limited set is expressed in EBV–growth transformed B cells, termed lymphoblastoid cell lines (LCLs). These cells proliferate via the concerted action of EBV nuclear antigens (EBNAs) and latent membrane proteins (LMPs), some of which are rate limiting to establish a stable homeostasis of growth promoting and anti-apoptotic activities. We show here that EBV mutants, which lack the EBNA-3A gene, are impaired but can still initiate cell cycle entry and proliferation of primary human B cells in contrast to an EBNA-2 deficient mutant virus. Surprisingly, and in contrast to previous reports, these viral mutants are attenuated in growth transformation assays but give rise to permanently growing EBNA-3A negative B cell lines which exhibit reduced proliferation rates and elevated levels of apoptosis. Expression profiles of EBNA-3A deficient LCLs are characterized by 129 down-regulated and 167 up-regulated genes, which are significantly enriched for genes involved in apoptotic processes or cell cycle progression like the tumor suppressor gene p16/INK4A, or might contribute to essential steps of the viral life cycle in the infected host. In addition, EBNA-3A cellular target genes remarkably overlap with previously identified targets of EBNA-2. This study comprises the first genome wide expression profiles of EBNA-3A target genes generated within the complex network of viral proteins of the growth transformed B cell and permits a more detailed understanding of EBNA-3A's function and contribution to viral pathogenesis

A randomized trial of a transglutaminase 2 inhibitor for celiac disease

BACKGROUND In celiac disease, small intestinal transglutaminase 2 causes deamidation of glutamine residues in gluten peptides, which enhances stimulation of T cells and leads to mucosal injury. Inhibition of transglutaminase 2 is a potential treatment for celiac disease. METHODS In a proof-of-concept trial, we assessed the efficacy and safety of a 6-week treatment with ZED1227, a selective oral transglutaminase 2 inhibitor, at three dose levels as compared with placebo, in adults with well-controlled celiac disease who underwent a daily gluten challenge. The primary end point was the attenuation of gluten-induced mucosal damage, as measured by the ratio of villus height to crypt depth. Secondary end points included intraepithelial lymphocyte density, the Celiac Symptom Index score, and the Celiac Disease Questionnaire score (for assessment of health-related quality of life). RESULTS Of the 41 patients assigned to the 10-mg ZED1227 group, the 41 assigned to the 50-mg group, the 41 assigned to the 100-mg group, and the 40 assigned to the placebo group, 35, 39, 38, and 30 patients, respectively, had adequate duodenal-biopsy samples for the assessment of the primary end point. Treatment with ZED1227 at all three dose levels attenuated gluten-induced duodenal mucosal injury. The estimated difference from placebo in the change in the mean ratio of villus height to crypt depth from baseline to week 6 was 0.44 (95% confidence interval [CI], 0.15 to 0.73) in the 10-mg group (P=0.001), 0.49 (95% CI, 0.20 to 0.77) in the 50-mg group (P<0.001), and 0.48 (95% CI, 0.20 to 0.77) in the 100-mg group (P<0.001). The estimated differences from placebo in the change in intraepithelial lymphocyte density were -2.7 cells per 100 epithelial cells (95% CI, -7.6 to 2.2) in the 10-mg group, -4.2 cells per 100 epithelial cells (95% CI, -8.9 to 0.6) in the 50-mg group, and -9.6 cells per 100 epithelial cells (95% CI, -14.4 to -4.8) in the 100-mg group. Use of the 100-mg dose may have improved symptom and quality-of-life scores. The most common adverse events, the incidences of which were similar across all groups, were headache, nausea, diarrhea, vomiting, and abdominal pain. Rash developed in 3 of 40 patients (8%) in the 100-mg group. CONCLUSIONS In this preliminary trial, treatment with ZED1227 attenuated gluten-induced duodenal mucosal damage in patients with celiac disease.publishedVersionPeer reviewe