The Qurʾan and Arabic Poetry

This chapter reviews recent scholarship on the interface between the Qur’an and Arabic Poetry, from pre-Islamic times to the modern period. It shows that Arabic poetry has for long been engaged in an inter-textual dialogue with the Qur’an which has taken numerous forms, subject to changing historical and cultural circumstances. At the core is the dual status of the Arabic language as bearer of a divinely created message and as cherished medium of poetic invention. The chapter shows that the resulting tension between the competing and mutually reinforcing claims of poetry and prophecy can be observed throughout the history of Arabic poetry up to the present day

Monitoring Three-Dimensional Packings in Microgravity

We present results from experiments with granular packings in three dimensions in microgravity as realized on parabolic flights. Two different techniques are employed to monitor the inside of the packings during compaction: (1) X-ray radiography is used to measure in transmission the integrated fluctuations of particle positions. (2) Stress-birefringence in three dimensions is applied to visualize the stresses inside the packing. The particle motions below the transition into an arrested packing are found to produce a well agitated state. At the transition, the particles lose their energy quite rapidly and form a stress network. With both methods, non-arrested particles (rattlers) can be identified. In particular, it is found that rattlers inside the arrested packing can be excited to appreciable dynamics by the rest-accelerations (g-jitter) during a parabolic flight without destroying the packings. At low rates of compaction, a regime of slow granular cooling is identified. The slow cooling extends over several seconds, is described well by a linear law, and terminates in a rapid final collapse of dynamics before complete arrest of the packing.Comment: 8 pages, 8 figure

Mannerism in Arabic literature: A structural analysis of selected poetry 3rd century AH/9th century AD-5th century AH/11th century AD.

The thesis contains six chapters; introduction, four chapters on selected works by four poets, and conclusion. The Arabic texts discussed are added as an appendix and numbered from I to XIX. Chapter One discusses the form and function of the panegyric qasida in the early Abbasid period. The organic unity of the individual poem is postulated in a structural model which serves as a working hypothesis for subsequent analyses. Chapters Two and Three contrast panegyrics by Buhturi (d. about 284 AH/897 AD) and Mihyar al-Daylami (d. 428 AH/ 1036 AD). Three poems by Buhturi are analysed with particular attention to the structural function of the initial section. A work by Mihyar, shown to follow similar principles of construction, is explored with respect to imagery. A comparison of two selected passages highlights stylistic differences between the two poets. Chapters Four and Five are devoted to ascetic poetry, contrasting the zuhdiyyat of Abu' l-'Atahiya (d. 213 AH/828 AD) and the Luzumiyyat of Abu'l-'Ala' al-Ma'arri (d. 449 AH/1058 AD). Chapter Four begins with a study of the origins of the zuhdiyya canon in the poetic tradition and its relation to the panegyric. Chapter Five focuses on the reinterpretation of the poetic tradition in Ma'arri's work. Both chapters conclude with the analysis of a selected text. Departing from the postulated unity of the individual poem, the analyses reveal the unity of the poetic corpus. The former is substantiated by recurring techniques of construction, the latter suggested by recurring motifs in contrasting contexts. It follows that the qasida, on the basis of one structural model, provides scope for combinations of motifs drawn from the entire poetic corpus. The analyses of chapters Two to Five provide the basis for a hypothesis on the nature of mannerism and classicism which the final chapter develops in reference to the debate on mannerism in Arabic literature. The hypothesis is tested by a return to the selected texts

Functional inhibition of acid sphingomyelinase by Fluphenazine triggers hypoxia-specific tumor cell death

Owing to lagging or insufficient neo-angiogenesis, hypoxia is a feature of most solid tumors. Hypoxic tumor regions contribute to resistance against antiproliferative chemotherapeutics, radiotherapy and immunotherapy. Targeting cells in hypoxic tumor areas is therefore an important strategy for cancer treatment. Most approaches for targeting hypoxic cells focus on the inhibition of hypoxia adaption pathways but only a limited number of compounds with the potential to specifically target hypoxic tumor regions have been identified. By using tumor spheroids in hypoxic conditions as screening system, we identified a set of compounds, including the phenothiazine antipsychotic Fluphenazine, as hits with novel mode of action. Fluphenazine functionally inhibits acid sphingomyelinase and causes cellular sphingomyelin accumulation, which induces cancer cell death specifically in hypoxic tumor spheroids. Moreover, we found that functional inhibition of acid sphingomyelinase leads to overactivation of hypoxia stress-response pathways and that hypoxia-specific cell death is mediated by the stress-responsive transcription factor ATF4. Taken together, the here presented data suggest a novel, yet unexplored mechanism in which induction of sphingolipid stress leads to the overactivation of hypoxia stress-response pathways and thereby promotes their pro-apoptotic tumor-suppressor functions to specifically kill cells in hypoxic tumor areas

Intraocular DHODH-inhibitor PP-001 suppresses relapsing experimental uveitis and cytokine production of human lymphocytes, but not of RPE cells

Background: Uveitis is a potentially blinding inflammatory disease of the inner eye with a high unmet need for new therapeutic interventions. Here, we wanted to investigate the suppressive effect of the intraocular application of the small molecule dihydroorotate dehydrogenase (DHODH)-inhibitor PP-001 on experimental relapsing rat uveitis and furthermore determine its effect on proliferation and cytokine secretion of human peripheral blood lymphocytes (PBL) and human retinal pigment epithelial (RPE) cells in vitro. Methods: Spontaneously relapsing uveitis was induced in rats by immunization with interphotoreceptor retinoid-binding protein (IRBP) peptide R14. PP-001 was injected intravitreally after resolution of the primary disease to investigate further relapses. Proliferation and metabolic activity of phytohemagglutinin (PHA)-stimulated human peripheral lymphocytes with and without PP-001 and cytokine secretion were determined by XTT assay and bioplex bead assay. The RPE cell line ARPE-19 as well as primary human RPE cells treated with PP-001 or anti-vascular endothelial growth factor (VEGF) antibody bevacizumab were also investigated for metabolic activity and cytokine/chemokine secretion. Results: Injection of PP-001 into rat eyes reduced the number of relapses by 70%, from 20 relapses (57% of the rats affected) in the control group to 6 relapses (33% of the rats) in the treatment group. In human PBL cultures, PP-001 reduced the proliferation in a dose-dependent manner. The secretion of several cytokines such as IL-17, IFN-gamma, and VEGF was suppressed by PP-001, as previously observed with rat T cells in the experimental autoimmune uveitis (EAU) model. In contrast, human RPE cells were not affected by PP-001, while the anti-VEGF antibody bevacizumab severely impaired the secretion of various cytokines including VEGF. Conclusions: For the first time, intravitreal injection of PP-001 demonstrated an effective, but transient reduction of relapses in the rat EAU model. In vitro PP-001 suppressed proliferation and cytokine/chemokine secretion of human lymphocytes, while neither human RPE cell line ARPE-19 nor primary RPE cells were affected

Mitochondrial Haplogroups and Control Region Polymorphisms in Age-Related Macular Degeneration: A Case-Control Study

Background: Onset and development of the multifactorial disease age-related macular degeneration (AMD) are highly interrelated with mitochondrial functions such as energy production and free radical turnover. Mitochondrial dysfunction and overproduction of reactive oxygen species may contribute to destruction of the retinal pigment epithelium, retinal atrophy and choroidal neovascularization, leading to AMD. Consequently, polymorphisms of the mitochondrial genome (mtDNA) are postulated to be susceptibility factors for this disease. Previous studies from Australia and the United States detected associations of mitochondrial haplogroups with AMD. The aim of the present study was to test these associations in Middle European Caucasians. Methodology/Principal Findings: Mitochondrial haplogroups (combinations of mtDNA polymorphisms) and mitochondrial CR polymorphisms were analyzed in 200 patients with wet AMD (choroidal neovascularization, CNV), in 66 patients with dry AMD, and in 385 controls from Austria by means of multiplex primer extension analysis and sequencing, respectively. In patients with CNV, haplogroup H was found to be significantly less frequent compared to controls, and haplogroup J showed a trend toward a higher frequency compared to controls. Five CR polymorphisms were found to differ significantly in the two study populations compared to controls, and all, except one (T152C), are linked to those haplogroups. Conclusions/Significance: It can be concluded that haplogroup J is a risk factor for AMD, whereas haplogroup H seems t

Global prevalence and genotype distribution of hepatitis C virus infection in 2015 : A modelling study

Publisher Copyright: © 2017 Elsevier LtdBackground The 69th World Health Assembly approved the Global Health Sector Strategy to eliminate hepatitis C virus (HCV) infection by 2030, which can become a reality with the recent launch of direct acting antiviral therapies. Reliable disease burden estimates are required for national strategies. This analysis estimates the global prevalence of viraemic HCV at the end of 2015, an update of—and expansion on—the 2014 analysis, which reported 80 million (95% CI 64–103) viraemic infections in 2013. Methods We developed country-level disease burden models following a systematic review of HCV prevalence (number of studies, n=6754) and genotype (n=11 342) studies published after 2013. A Delphi process was used to gain country expert consensus and validate inputs. Published estimates alone were used for countries where expert panel meetings could not be scheduled. Global prevalence was estimated using regional averages for countries without data. Findings Models were built for 100 countries, 59 of which were approved by country experts, with the remaining 41 estimated using published data alone. The remaining countries had insufficient data to create a model. The global prevalence of viraemic HCV is estimated to be 1·0% (95% uncertainty interval 0·8–1·1) in 2015, corresponding to 71·1 million (62·5–79·4) viraemic infections. Genotypes 1 and 3 were the most common cause of infections (44% and 25%, respectively). Interpretation The global estimate of viraemic infections is lower than previous estimates, largely due to more recent (lower) prevalence estimates in Africa. Additionally, increased mortality due to liver-related causes and an ageing population may have contributed to a reduction in infections. Funding John C Martin Foundation.publishersversionPeer reviewe