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We discuss the potential of light-nuclei measurements in heavy-ion collisions at intermediate energies for the search of the hypothetical QCD critical end-point. A previous proposal based on neutron density fluctuations has brought appealing experimental evidences of a maximum in the ratio of the number of tritons times protons, divided over deuterons square, O tpd. However these results are difficult to reconcile with the state-of-the-art statistical thermal model predictions. Based on the idea that the QCD critical point can lead to a substantial attraction among nucleons, we propose new light-nuclei multiplicity ratios involving He in which the maximum would be more noticeable. We argue that the experimental extraction is feasible by presenting these ratios formed from actual measurements of total and differential yields at low and high collision energies from FOPI and ALICE experiments, respectively. We also illustrate the possible behavior of these ratios at intermediate energies applying a semiclassical method based on flucton paths using the preliminary NA49 and STAR data for O tpd as input.
A new phylogenetic hypothesis is proposed for the relationships among the species within the genus Docosia Winnertz, 1863, based on a combined analysis of five DNA markers (28S, ITS2, COI, COII and CytB). Five new species are described, Docosia anatolica Ševčík sp. nov. from Turkey, D. japonica Kurina sp. nov. from Japan, D. peloponnensis Ševčík sp. nov. from Greece, D. svanetica Kurina sp. nov. from Caucasus and D. polyspina Kurina sp. nov. from the Russian Far East. New country records of the following species are presented: D. diutina Plassmann, 1996 (Turkey), D. flavicoxa Strobl, 1900 (Georgia), D. gilvipes (Haliday in Walker, 1856) (Georgia), D. kerkini Kurina & Ševčík, 2011 (Bulgaria), D. moravica Landrock, 1916 (Georgia), D. pannonica Lastovka & Ševčík 2006 (Georgia) and D. rameli Kurina & Ševčík, 2011 (Slovakia).
Spinocerebellar ataxia type 2 (SCA2) is an autosomal dominant neurodegenerative movement disorder caused by expansion of CAG repeats in the ATXN2 gene beyond 33 units, while healthy individuals carry 22-23 repeats. First symptoms of SCA2 include uncoordinated movement, ataxic gait and slowing of the saccadic eye movements in line with the early pronounced atrophy of cerebellum, spinal cord and brainstem. Cerebellar Purkinje cells and spinal cord motor neurons are the most affected cells from ATXN2 expansions. Later on, patients manifest distal amyotrophy, problems in breathing and swallowing, depression and cognitive decline caused by widespread degeneration throughout the brain. The striking loss of mass in the brain, due to severe myelin fat atrophy, is accompanied by a similar reduction in the peripheral fat stores. After the devastating progression of disease, the severity and duration of which depends on the CAG repeat size, genetic background and environmental factors, patients succumb to SCA2 mostly because of respiratory failure at the terminal stage. Larger repeat sizes lead to an earlier manifestation of the disease and a more rapid progression. Aside from SCA2, intermediate-length and short pathogenic CAG expansions in ATXN2 between 26-39 repeats significantly increase the risk of developing other neurodegenerative disorders, such as amyotrophic lateral sclerosis (ALS), fronto-temporal lobar dementia (FTLD) or Parkinson plus tauopathies like progressive supranuclear palsy (PSP) in various cohorts across the world.
Ataxin-2 (ATXN2) is a ubiquitously expressed cytosolic protein most famous for its involvement in neurodegenerative disease caused by the expanded poly-glutamine (polyQ) domain corresponding to a genomic (CAG)n tract. This N-terminal polyQ domain has no known function, other than increasing the aggregation propensity of mutant ATXN2 and facilitating interaction with other polyQ containing proteins, leading to their sequestration. The progressive accumulation of ATXN2 into cytosolic foci, and also that of its interaction partners over time, underlies the molecular pathomechanism. Next to polyQ domain, ATXN2 also contains a Like-Sm domain (Lsm), an Lsm-associated domain (LsmAD), multiple proline-rich domains (PRD) and a Poly(A)-Binding-Protein (PABP)-interacting motif (PAM2).
Through its Lsm/LsmAD domains, ATXN2 directly binds to a large number of transcripts, regulating their quality and translation rate. In a similar fashion, through its direct interaction with PABP via PAM2 motif, ATXN2 indirectly modifies the fate of even larger number of transcripts and global translation. Several PRDs scattered across the protein help ATXN2 associate with growth factor receptors and other endocytosis factors, modulating nutrient uptake and downstream signaling.
ATXN2 is a stress response factor. Therefore, its involvement in nutrient uptake plays a crucial part in cell’s capability to overcome non-permissive conditions. Upon nutrient deprivation, oxidative stress, proteotoxicity, heat stress or Ca2+ imbalance, ATXN2 relocalizes into cytosolic ribonucleoprotein particles known as stress granules (SGs), together with PABP, several eukaryotic translation initiation factors, many other RNA-binding proteins (RBP) with their target transcripts and the small ribosomal subunit. Collectively, they modulate the stability of the trapped transcripts, favoring the maturation and translation of IRES-dependent stress response proteins instead, according to the specific need. Many RBPs interact either directly or in an RNA-dependent manner in the SGs, and due to the large number of ALS-causing mutations identified in them (such as TDP-43, FUS, TIA-1, hnRNPA2/B1), SGs became a hot topic in neuropathology. Acute SGs serve to halt translation and growth, and to spend energy only for survival until stress disappears. However, chronic SG assembly eventually activates apoptotis leading to cell death. While the polyQ expansions in ATXN2 enhance SG stability, reduce their dissociation rate after stress, and lead to aberrant post-translational modifications of other SG components like TDP-43, complete loss of ATXN2 delays SG formation and results in easily dissolvable foci.
Most of the stressors that induce SG formation eventually converge on energetic deficit. Therefore, it is logical that the ultimate task of SGs is to stop further growth when it cannot be afforded. In yeast, the molecular mechanism underlying this growth arrest was explained as sequestration of the master growth regulator complex, Target-of-Rapamycin Complex 1 (TORC1), into SGs in an ATXN2-dependent manner. The repressor effect of ATXN2 on mammalian TORC1 (mTORC1) and global protein translation had already been documented in earlier studies; complete loss of ATXN2 function in knock-out mouse (Atxn2-KO) resulted in mTORC1 hyperactivity and transcriptional upregulation of multiple ribosomal subunits indicating an increased need for these machines. ...
Türkiye'de 1998 yılından bu yana üniversitelerde lisans düzeyinde uygulanmakta olan Çift Anadal Programları, şartları sağlayabilen öğrencilere iki ayrı anadaldan aynı zamanda mezun olma şansı tanımaktadır. Bu çalışmada, bu programları bütün yönleri ile Almanca Öğretmenliği bölümlerinin gözünden incelemek amaçlanmıştır. Buna yönelik olarak veri toplamak için bir anket geliştirilmiş ve bu anket Türkiye'deki altı üniversitenin Almanca Öğretmenliği Programı öğrencisi olan 513 kişi üzerinde uygulanmıştır. Anket sonuçlarına göre çift anadala katılımcıların ilgisi beklenilenin çok üstündedir. Katılımcılar özellikle ileride atanma şanslarını çift diploma sayesinde artırmak için çift anadal yapmak istediklerini belirtmişlerdir. Ayrıca katılımcıların büyük bir çoğunluğu İngilizce Öğretmenliği bölümünde çift anadal yapmak isterken bu seçimin başlıca nedenleri olarak katılımcıların İngilizce dil bilgilerinin iyi olması ve bu bölümün atanma oranlarının yüksek olması bulunmuştur. Katılımcılar, çift anadal sayesinde disiplinlerarası çalışma becerilerinin gelişmesine ve çift anadalın hem mesleki hem de bilişsel birçok faydası olduğuna da işaret etmişlerdir. Bununla beraber çift anadal yapmak katılımcılar tarafından stresli, zaman açısından ve iş yükü bakımından zor bir program olarak değerlendirilmiştir. Çalışmanın sonuçlarına göre çift anadalın daha da geliştirilmesi ve sorunlarının ortadan kaldırılmasına yönelik bazı öneriler verilmiştir.
This work presents, to our knowledge, the first completely passive imaging with human-body-emitted radiation in the lower THz frequency range using a broadband uncooled detector. The sensor consists of a Si CMOS field-effect transistor with an integrated log-spiral THz antenna. This THz sensor was measured to exhibit a rather flat responsivity over the 0.1–1.5-THz frequency range, with values of the optical responsivity and noise-equivalent power of around 40 mA/W and 42 pW/√Hz, respectively. These values are in good agreement with simulations which suggest an even broader flat responsivity range exceeding 2.0 THz. The successful imaging demonstratestheimpressivethermalsensitivitywhichcanbeachievedwithsuchasensor. Recording of a 2.3×7.5-cm2-sized image of the fingers of a hand with a pixel size of 1 mm2 at a scanning speed of 1 mm/s leads to a signal-to-noise ratio of 2 and a noise-equivalent temperature difference of 4.4 K. This approach shows a new sensing approach with field-effect transistors as THz detectors which are usually used for active THz detection.
Genel Edebiyat Biliminin bir dalı olan "Karşılaştırmalı Edebiyat", farklı dillerde yazılmış edebi eserlerin, benzerlik ve farklılıklar yönünden karşılaştırılmasıdır. Karşılaştırmaya dayalı analizlerdeki amaç, iki ya da daha fazla eserin, biçim, üslup, motif ve ya tema gibi edebi unsurlar açısından ortak ve ya farklı öğelerini belirlemektir. Edebi metinlerde kullanılan dilsel öğeleri inceleme alanı olan "Biçembilim", okuyucunun metinleri anlamasını sağlayan en önemli araçlardan biridir. Karşılaştırmalı Edebiyat bilimi kapsamında çevirinin önemi yadsınamaz ve bir metin ile çevirisi, mukayeseli çalışma alanlarından biridir. Bu araştırmanın özünü, kaynak metin ve erek metin arasındaki benzerlik ve farklılıkları örneklendirmek adına karşılaştırmalı edebi çeviri örneği oluşturmaktadır. Bu bağlamda, bu çalışmada, William Shakespeare'in "Sonnet 66" şiirinin Türk edebiyatçı Can Yücel tarafından "66. Sone" olarak çevirisinin, Katharina Reiss'in "içerik odaklı" çeviri modeline dayanarak nasıl yorumlandığı incelenmiştir.
Evrensel bir konu olan savaş, her milleti derinden etkileyen en önemli olgulardan sayılmaktadır ve yansıması Karşılaştırmalı Edebiyatın en seçkin konularından biridir. Savaşlar yüzünden birçok farklı kültürde, toplumsal dengeler bozulmuş, cinsiyetçi roller değişmiş ve "yeni kadın" olgusu öne çıkmıştır. Bu çalışmada, 20. yüzyılın kadın Türk edebiyatçılarından biri olan Halide Edip Adıvar'ın 'Ateşten Gömlek' (1922) romanında ve İngiliz edebiyatçı David Herbert Lawrence'ın 'Tilki' ('The Fox') (1922) hikâyesinde "yeni kadın" kavramı karşılaştırmalı edebiyat yöntemi ile analiz edildi. Her iki eserin yansıttığı dönemin tarihsel ve sosyal örgüsü metin inceleme yöntemi ile incelendi. Çalışmanın özü, toplumsal cinsiyet rollerinin savaş dönemlerinde farklı kültürlerin edebiyatlarındaki yansımasını kapsar. İncelemedeki bulguların sonucunda, farklı kültürlerde farklı cinsiyetlere ait yazarlar tarafından ele alınmış olsa da, Adıvar'ın 'Ateşten Gömlek' ve Lawrence'ın 'Tilki' adlı eserinde, savaşın cinsiyet rollerine etkisinin benzer şekilde yansıtıldığı gözlenmiştir. Bu sebeple, bu çalışma, diğer karşılaştırmalı edebi incelemelere ve savaş edebiyatında kadın kimliğinin tanımlanmasına yönelik araştırmalara katkı sağlayabilecek içeriktedir.
Joseph Roth, ein Autor, dessen Werke der sogenannten deutschsprachigen österreichischen Exilliteratur zugeschrieben werden können, stellt in seinem Roman "Das falsche Gewicht" 1937, die Geschichte eines Eichmeisters dar, der nach viele Jahren Militärdienst einem Grenzgebiet namens Zlotogrod zugeteilt wurde. Die Arbeit beschäftigt sich mit der Heimatauffassung Galiziens im dargestellten Werk und untersucht nach einem kurzen Überblick die Bedeutung des Wortes Heimat und Schlüsselbereiche wie Heimatromane und das typologische Modell des traditionellen Heimatromans. Die allgemeinen Aspekte des Heimatromans fußen weitgehend auf Karlheinz Rossbachers Auffassung, die von Andrea Kunne weitläufig vorangetrieben wurde. Die Aufteilung von Kunne in zwei vereinfachte Gruppen berücksichtigt nur die grundlegendsten Merkmale dieses Genres und wird daher ausschließlich für den Zweck dieser Studie verwendet. Im zweiten Schritt werden Vergleiche und Analysen anhand von Beispielen aus dem Werk des Autors durchgeführt. Ziel ist es daher, das Werk des Autors zu untersuchen und aufzuzeigen, wie die Kritik des betreffenden Landes durch die literarische Kunst reflektiert wird. Schließlich wird eine Auswertung der Ergebnisse veranschaulicht.
Namen sind seit Jahrhunderten ein wichtiger Bestandteil des Lebens der Menschen. Die Auswahl eines geeigneten Namens spielt für viele Eltern eine große Rolle für ihr Kind. Infolgedessen ist die Benennung nach der Geburt für alle Kulturen ein äußerst wichtiges Ereignis. In der vorliegenden Arbeit werden Vornamen im Deutschen und im Türkischen untersucht, die aus Blumennamen stammen. Das Ziel ist es, herauszufinden, aus welchen Sprachen die Vornamen mit Blumennamen ins Türkische und Deutsche entlehnt worden sind, und ob es Parallelen und Unterschiede bei der Frequenz der entlehnten Vornamen aus unterschiedlichen Sprachen und beim Gebrauch von bestimmten Blumenarten gibt.
Es ist nicht zu übersehen, dass Migration und Flucht seit langem in Deutschland als Problem und besonders Integration für den sozialen Zusammenhalt als unbedingt notwendig dargestellt werden. Weder die Einheimischen noch die Einwanderer hatten von der Sprache und Kultur voneinander viel Ahnung und die Einheimischen verlangten bald die Integration, da sie dachten, dass alle Probleme, die die Arbeitsmigranten und Flüchtlinge verursachten, durch die Integration gelöst würden, und ein friedliches Zusammenleben in diesen Sprach- und Kulturkonflikten ermöglicht würde. So wurde das Wort "Integration" in Deutschland seit den 70er Jahren ein Zentralbegriff in der Migration. Es ist auch erfreulich zu beobachten, wie immer mehr deutsche AutorInnen die Migranten-und Flüchtlingskinder, ihr Konfliktpotential und ihre Integration in die deutsche Gesellschaft in ihren Werken behandeln, die zur Zeit in der problemorientierten realistischen Kinder- und Jugendliteratur einen wichtigen Platz einnehmen. Der vorliegende Beitrag konzentriert sich einerseits auf die aktuelle deutsche Kinder- und Jugendliteratur, in der es um Kinder und Jugendliche mit Migrations- und Fluchthintergrund geht, andererseits wird versucht, anhand der literarischen Textanalysen ausgewählter Kinder- und Jugendbücher aufzuzeigen, ob die Integrationsbestrebungen dieser Kinder und Jugendlichen erfolgreich waren oder gescheitert sind.
Johannes Schiltberger, 1394-1427 yılları arasında Türkiye, Suriye, Mısır, İran, Orta Asya ve Sibirya'da esir olarak yaşayıp gördüklerini "Türkler ve Tatarlar Arasında (1394-1427)" başlıklı kitabında yazıya geçirir. Çok değişik insan coğrafyalarında bulunmuş olmasından dolayı Schiltberger'in Türkleri insani özellikleri bakımından diğer halklarla karşılaştırma yoluna gideceğini varsayıyoruz. Hans Ulrich Krafft ise 24 Ağustos 1574 yılında borç yüzünden Osmanlı-Türk makamlarınca tutuklanır. 24 Ağustos 1577 yılında tahliye edilir ve memleketine dönmek üzere yola çıkar ve ancak 9 Aralık 1578'de vatanına kavuşur. Mesleği tacirlik olan H. U. Krafft'ın Osmanlı toplumunda geçerli ticaret ve ticari ilişkiler hakkında hassasiyeti olacağından, gözlemlerinde bunlara yer vereceğini düşünüyoruz. Bu makalede her iki Almanın anılarında İstanbul'un fethi öncesi ve sonra sosyal hayatta gözlemlenen değerler ve değer yargıları ele alınacaktır. Öncelikle sosyal, ahlaki, insani değerler her bir eserde tespit edilecek, sonra bunlar 150 yıllık süre bağlamında karşılaştırılarak Osmanlı-Türk Toplumunda değerler değişimi olup olmadığı ve var ise bunların olası nedenleri üzerinde duracağız.
Bundan 61 yıl önce, 1959 yılında Eskişehir Maarif Koleji binasında Milli Eğitim Bakanlığı'na bağlı olarak gece eğitimi vermek üzere üç yıllık bir Yabancı Diller Yüksekokulu (MEB YDYO) kuruldu. Okul İngilizce Bölümü'nden müteşekkildi. Yüksekokulun müdürlüğünü de İngilizce öğretmeni Ahmet Cemal AŞAN yapıyordu. Onun yardımcılığına da Almanca öğretmeni Okt. Recep GÖK atanmıştı. 1980-1981 eğitim öğretim yılında ilk öğrencilerini alan Almanca Bölümü'nde Almanca öğretmeni Seyyare DUMAN ve Ali GÜLTEKİN de öğretim görevlisi olarak ders veriyorlardı.
Evidence is increasingly pointing towards a significant global decline in biodiversity. The drivers of this decline are numerous, including habitat change and overexploitation, rapid deforestation, pollution, exotic species and disease, and finally climate change as an emerging driver of biodiversity change (Nakamura, et al., 2013; Hancocks, 2001; Pereira, Navarro & Martins, 2012). Raising public awareness of the need to conserve biological diversity is essential to safeguard the richness of life forms all over the world (Lindemann-Matthies, 2002). In this regard, institutions such as science museums, zoos and aquariums have the potential to play an important role (Rennie & Stocklmayer, 2003). Especially, zoos can provide a productive learning environment (Miles & Tout, 1992), facilitating the promotion of public conservation awareness and the adoption of pro-environmental behaviours that would reduce negative human impacts on biodiversity (Barongi, et al., 2015).
Based on these concepts, my study contributes to the developing field of visitor studies. Taking as reference non-zoo visitors and zoo visitors, I have focused on reviewing some aspects of conservation education, such as people's awareness of conservation, people's interest in animals and people's feelings towards animals and attitudes towards zoos. The study identified differences between non-regular and regular zoo visitors in interests in animals, as well as visitor attitudes towards conservation issues and zoos. Therefore, the present study indicated that positive emotional reactions and, in particular, a perceived sense of connection to the animal were linked and depended on the frequency of zoo visits. It was as well remarkable, that conservation awareness was influenced by the interest in animals, the interest in visiting zoos, the attitudes towards these institutions, and the age and the country of origin. All these variables had a greater effect in the conservation consciousness of the participants. Additionally interestingly, the main reason for visiting zoos in every country was to learn something about animals. This highlights the educational role of zoos and broadly supports the idea that people want to visit zoos to learn something about animals, in turn facilitating pro-conservation learning and changes in attitude. They are uniquely positioned to interact with visitors, communities, and society and to contribute by providing an informative and entertaining environment. Visiting zoos could led to contribute to promoting animal connectedness and interest in species.
Recent data have suggested that performing recanalizing therapies in ischemic stroke might lead to an increased risk of acute symptomatic seizures. This applies to both intravenous thrombolysis and mechanical thrombectomy. We therefore determined the frequency of acute symptomatic seizures attributable to these two recanalization therapies using a large, population-based stroke registry in Central Europe. We performed two matched 1:1 case–control analyses. In both analyses, patients were matched for age, stroke severity on admission and pre-stroke functional status. The first analysis compared patients treated with intravenous thrombolysis to a non-recanalization control group. To isolate the effect of mechanical thrombectomy, we compared patients with both mechanical thrombectomy and intravenous thrombolysis to those with only intravenous thrombolysis treatment in a second analysis. From 135,117 patients in the database, 13,356 patients treated with only intravenous thrombolysis, and 1013 patients treated with both intravenous thrombolysis and mechanical thrombectomy were each matched to an equivalent number of controls. Patients with intravenous thrombolysis did not suffer from clinically apparent acute symptomatic seizures significantly more often than non-recanalized patients (treatment = 199; 1.5% vs. control = 237; 1.8%, p = 0.07). Mechanical thrombectomy in addition to intravenous thrombolysis also was not associated with an increased risk of acute symptomatic seizures, as the same number of patients suffered from seizures in the treatment and control group (both n = 17; 1.7%, p = 1). In a large population-based stroke registry, the frequency of clinically apparent acute symptomatic seizures was not increased in patients who received either intravenous thrombolysis alone or in conjunction with mechanical thrombectomy.
The National Institutes of Health Stroke Scale (NIHSS) score is the most frequently used score worldwide for assessing the clinical severity of a stroke. Prior research suggested an association between acute symptomatic seizures after stroke and poorer outcome. We determined the frequency of acute seizures after ischemic stroke in a large population-based registry in a central European region between 2004 and 2016 and identified risk factors for acute seizures in univariate and multivariate analyses. Additionally, we determined the influence of seizures on morbidity and mortality in a matched case–control design. Our analysis of 135,117 cases demonstrated a seizure frequency of 1.3%. Seizure risk was 0.6% with an NIHSS score at admission <3 points and increased up to 7.0% with >31 score points. Seizure risk was significantly higher in the presence of acute non-neurological infections (odds ratio: 3.4; 95% confidence interval: 2.8–4.1). A lower premorbid functional level also significantly increased seizure risk (OR: 1.7; 95%CI: 1.4–2.0). Mortality in patients with acute symptomatic seizures was almost doubled when compared to controls matched for age, gender, and stroke severity. Acute symptomatic seizures increase morbidity and mortality in ischemic stroke. Their odds increase with a higher NIHSS score at admission.
A systematic review on the burden of illness in individuals with tuberous sclerosis complex (TSC)
(2020)
Objective: This review will summarize current knowledge on the burden of illness (BOI) in tuberous sclerosis complex (TSC), a multisystem genetic disorder manifesting with hamartomas throughout the body, including mainly the kidneys, brain, skin, eyes, heart, and lungs.
Methods: We performed a systematic analysis of the available literature on BOI in TSC according to the PRISMA guidelines. All studies irrespective of participant age that reported on individual and societal measures of disease burden (e.g. health care resource use, costs, quality of life) were included.
Results: We identified 33 studies reporting BOI in TSC patients. Most studies (21) reported health care resource use, while 14 studies reported quality of life and 10 studies mentioned costs associated with TSC. Only eight research papers reported caregiver BOI. Substantial BOI occurs from most manifestations of the disorder, particularly from pharmacoresistant epilepsy, neuropsychiatric, renal and skin manifestations. While less frequent, pulmonary complications also lead to a high individual BOI. The range for the mean annual direct costs varied widely between 424 and 98,008 International Dollar purchasing power parities (PPP-$). Brain surgery, end-stage renal disease with dialysis, and pulmonary complications all incur particularly high costs. There is a dearth of information regarding indirect costs in TSC. Mortality overall is increased compared to general population; and most TSC related deaths occur as a result of complications from seizures as well as renal complications. Long term studies report mortality between 4.8 and 8.3% for a follow-up of 8 to 17.4 years.
Conclusions: TSC patients and their caregivers have a high burden of illness, and TSC patients incur high costs in health care systems. At the same time, the provision of inadequate treatment that does not adhere to published guidelines is common and centralized TSC care is received by no more than half of individuals who need it, especially adults. Further studies focusing on the cost effectiveness and BOI outcomes of coordinated TSC care as well as of new treatment options such as mTOR inhibitors are necessary.
This Dissertation deals with the development of FAIR-relevant X-ray diagnostics based on the interaction of lasers and particle beams with matter. The associated experimental methods are supposed to be employed in the HIHEX-experiments in the HHT-cave of the GSI Helmholtz Center for Heavy-Ion Research GmbH (GSI) in Phase-0 and in the APPA-cave at the Facility for Antiproton and Ion Research in Darmstadt, Germany.
Diagnostic of high aerial density targets that will be used in FAIR experiments demands intense and highly penetrating X-ray sources. Laser generated well-directe relativistic electron beams that interact with high Z materials is an excellent tool for generation of short-pulse high luminous sources of MeV-gammas.
In pilot experiments carried out at the PHELIX laser system, GSI Darmstadt, relativistic electrons were produced in a long scale plasma of near critical electron density (NCD) by the mechanism of the direct laser acceleration (DLA). Low density polymer foam layers preionised by a well-defined nanosecond laser pulse were used as NCD targets. The analysis of the measured electron spectra showed up to 10- fold increase of the electron "temperature" from T_Hot = 1–2 MeV, measured for the case of the interaction of 1–2 ×10^19 Wcm^(−2) ps-laser pulse with a planar foil, up to 14 MeV for the case when the relativistic laser pulse propagates through the by a ns-pulse preionised foam layer. In this case, up to 80–90 MeV electron energy was registered. An increase of the electron energy was accompanied by a strong increase of the number of relativistic electrons and well-defined directionality of the relativistic electron beam measured to be (12 ±1)° (FWHM). This directionality increases the gamma flux on target by far compared to the soft X-ray sources.
Additionally to laser based active diagnostics, passive techniques involving inherent X-ray fluorescence radiation of projectile and target emitted during heavy-ion target interaction can be used to measure the ion beam distribution on shot. This information is of great importance, since the target size is chosen to be smaller than the beam focus in order to ensure homogeneous heating of the HIHEX-target by the ion beam. High amounts of parasitic radiation and activation of experimental equipment is expected for experiments at the APPA-cave. For this reason, all electronic devices must be placed at a safe distance to the target chamber. In order to transport the signal over a large distance, the X-ray image of the target irradiated by heavy-ions has to be converted into an optical one.
For these purposes, the X-ray Conversion to Optical radiation and Transport (XCOT)-system was developed in the frame of a BMBF-project and commissioned in two beamtimes at the UNILAC, GSI during this work.
In experiments, we observed intense radiation of target atoms (K-shell transitions in Cu at 8–8.3 keV and L-shell transition in Ta) ionised in collisions with heavy ions as well as Doppler-shifted L-shell transitions of Au-projectiles passing through targets. This radiation can be used for monochromatic (dispersive elements like bent crystals) or polychromatic (pinhole) 2D X-ray mapping of the ion beam intensity distribution in the interaction region during the beam-target interaction. We measured the efficiency of the X-ray photon production depending on the target thickness and the number of ions passing through the target. The spatial resolution of the XCOT-system based on the multi-pinhole camera was measured to be (91±17) μm for the image magnification factor M = 2. It was considerably improved by application of a toroidally bent quartz crystal and reached 30 μm at M = 6. This resolution is optimal to image the distribution of a 1mm in diameter ion beam. As next step, the XCOT-system will be tested during the SIS18 beam-time at the HHT-experimental area.
The purpose of this study was to identify distinctive mental health profiles for industrial psychologists based on the Mental Health Continuum. Further, it aimed to determine how these profiles differ with respect to work-role fit, meaningfulness and work engagement. It also aimed to investigate whether industrial psychologists within managerial or specialist differ in respect of different types of mental health. An online cross-sectional survey design was employed to draw a census sample (n = 274) from all South African industrial psychologists. A biographical questionnaire, the Work-Role Fit Scale, the Psychological Meaningfulness Scale, the Work Engagement Scale, and the Mental Health Continuum–Short Form were administered. Descriptive statistics, correlations, latent profile analysis, MANOVAs and ANOVAs were computed. Three mental health profiles for industrial psychologists were identified: languishing, moderately mentally healthy and flourishing. Significant differences between the three mental health profiles and experiences of meaningful work-role fit and work engagement were found, but not between experiences of managerial roles. The results show that individuals with different mental health profiles, experience work and its related outcomes, differently. Therefore, in order to enhance meaningful work-role fit and work engagement of industrial psychologists, a one-size-fits-all model may not be appropriate.
Editorial: Positive organizational interventions: contemporary theories, approaches and applications
(2020)
Despite the popularity of the term Positive Psychological Coaching within the literature, there is no consensus as to how it should be defined (framed) or what the components of a positive coaching “model” should include. The aim of this systematic review was to define positive psychological coaching and to construct a clear demarcated positive psychological coaching model based on the literature. A systematic literature review led to the extraction of 2,252 records. All records were screened using specific inclusion/exclusion criteria, which resulted in the exclusion of records based on duplicates (n = 1,232), titles (n = 895), abstracts (n = 78), and criteria violations (n = 23). Twenty-four academic, peer-reviewed publications on positive psychological coaching were included. Data relating to conceptual definitions and coaching models/phases/frameworks were extracted and processed through thematic content analysis. Our results indicate that positive psychological coaching can be defined as a short to medium term professional, collaborative relationship between a client and coach, aimed at the identification, utilization, optimization, and development of personal strengths and resources in order to enhance positive states, traits and behaviors. Utilizing Socratic goal setting and positive psychological evidence-based approaches to facilitate personal growth, optimal functioning, enhanced wellbeing, and the actualization of people's potential. Further, eight critical components of a positive psychological coaching model were identified and discussed. The definition and coaching process identified in this study will provide coaches with a fundamental positive psychological framework for optimizing people's potential.
The purpose of this study was to examine the psychometric properties (i.e., factorial validity, measurement invariance, and reliability) of the Grit-Original scale (Grit-O) within the Netherlands. The Grit-O scale was subjected to a competing measurement modeling strategy that sequentially compared both independent cluster model confirmatory factor analytical- and exploratory structural equation modeling approaches. The results showed that both a two first order, bi-factor structure as well as a less restrictive two factor ESEM factorial structure best-fitted the data. The instrument showed to be reliable at both a lower- (Cronbach’s alpha) and upper-level (composite reliability) limit. However, measurement invariance between genders could only be established for the B-ICM-CFA model. Finally, concurrent validity was established through relating the GRIT-O to task performance. The linear use of the Grit-O scale should therefore carefully be considered.
This article examines whether autonomy as an educational aim should be defended at the global scale. It begins by identifying the normative issues at stake in global autonomy education by distinguishing them from the problems of autonomy education in multicultural nation-states. The article then explains why a planet-wide expansion of the ideal of autonomy is conceivable on the condition that the concept of autonomy is widened in a way that renders its precise meaning flexibly adjustable to a variety of distinct social and cultural contexts. A context-transcendent, core meaning of autonomy remains in place, however, according to which a person is only autonomous if she relates to the values and goals that direct her life in a way so that she sees them as her own and is able to identify and critically assess her principal reasons for action. Finally, the article addresses two challenges to the global expansion of autonomy education: the objection that autonomy is presently not the most important educational aim and the objection that global autonomy education is a form of cultural imperialism. It finds both objections wanting.
This paper presents some results from a wider study which aims to define the features of German medical textbooks from a diachronic perspective. The medical textbook is presented here as a genre-class (Textsortenklasse) subsuming all texts written for didactic purposes in the field of medicine, i.e. texts aiming to present the theoretical and practical background required in this particular specialist professional field. Since the lingua franca of academic communication was Latin until the 18th century, the corpus used for this study mainly comprises surgery textbooks. The paper focuses solely on structural aspects of textbooks, seeking to show how these aspects functionally contribute to the realization of the general textual function and thereby constitute a historically established conventionalized scheme underlying genres. However, a thorough and effective description of a genre-class requires a much more extensive approach including more interrelated levels of analysis.
Background: Berotralstat (BCX7353) is an oral, once-daily inhibitor of plasma kallikrein in development for the prophylaxis of hereditary angioedema (HAE) attacks.
Objective: Our aim was to determine the efficacy, safety, and tolerability of berotralstat in patients with HAE over a 24-week treatment period (the phase 3 APeX-2 trial).
Methods: APeX-2 was a double-blind, parallel-group study that randomized patients at 40 sites in 11 countries 1:1:1 to receive once-daily berotralstat in a dose of 110 mg or 150 mg or placebo (Clinicaltrials.gov identifier NCT03485911). Patients aged 12 years or older with HAE due to C1 inhibitor deficiency and at least 2 investigator-confirmed HAE attacks in the first 56 days of a prospective run-in period were eligible. The primary efficacy end point was the rate of investigator-confirmed HAE attacks during the 24-week treatment period.
Results: A total of 121 patients were randomized; 120 of them received at least 1 dose of the study drug (n = 41, 40, and 39 in the 110-mg dose of berotralstat, 150-mg of dose berotralstat, and placebo groups, respectively). Berotralstat demonstrated a significant reduction in attack rate at both 110 mg (1.65 attacks per month; P = .024) and 150 mg (1.31 attacks per month; P < .001) relative to placebo (2.35 attacks per month). The most frequent treatment-emergent adverse events that occurred more with berotralstat than with placebo were abdominal pain, vomiting, diarrhea, and back pain. No drug-related serious treatment-emergent adverse events occurred.
Conclusion: Both the 110-mg and 150-mg doses of berotralstat reduced HAE attack rates compared with placebo and were safe and generally well tolerated. The most favorable benefit-to-risk profile was observed at a dose of 150 mg per day.
Die fragmentierte und scheinbar kontingente Struktur von Goethes Roman "Wilhelm Meisters Wanderjahre" folgt, so soll hier gezeigt werden, nicht zuletzt auch einem besonderen Zeitregime. Der Roman erprobt vor allem in seiner um Wilhelm und Lenardo gruppierten Handlung Formen des analeptischen Erzählens, das die Ereignisse nicht chronologisch-linear, sondern in wiederholten Rückgriffen und Zeitschleifen entwickelt. Dieses Erzählen 'von' und 'in' Vorgeschichten folgt einem Schema, das Goethe in den homerischen Epen vorgeprägt sieht, das aber auch mit Zeitreflexionen aus seinen geologischen Studien korrespondiert.
Aging is a one-way process associated with profound structural and functional changes in the organism. Indeed, the neuromuscular system undergoes a wide remodeling, which involves muscles, fascia, and the central and peripheral nervous systems. As a result, intrinsic features of tissues, as well as their functional and structural coupling, are affected and a decline in overall physical performance occurs. Evidence from the scientific literature demonstrates that senescence is associated with increased stiffness and reduced elasticity of fascia, as well as loss of skeletal muscle mass, strength, and regenerative potential. The interaction between muscular and fascial structures is also weakened. As for the nervous system, aging leads to motor cortex atrophy, reduced motor cortical excitability, and plasticity, thus leading to accumulation of denervated muscle fibers. As a result, the magnitude of force generated by the neuromuscular apparatus, its transmission along the myofascial chain, joint mobility, and movement coordination are impaired. In this review, we summarize the evidence about the deleterious effect of aging on skeletal muscle, fascial tissue, and the nervous system. In particular, we address the structural and functional changes occurring within and between these tissues and discuss the effect of inflammation in aging. From the clinical perspective, this article outlines promising approaches for analyzing the composition and the viscoelastic properties of skeletal muscle, such as ultrasonography and elastography, which could be applied for a better understanding of musculoskeletal modifications occurring with aging. Moreover, we describe the use of tissue manipulation techniques, such as massage, traction, mobilization as well as acupuncture, dry needling, and nerve block, to enhance fascial repair.
Die Bestimmung von Procalcitonin im Serum stellt einen wesentlichen Bestandteil der Diagnostik, Verlaufskontrolle und Therapieüberwachung septischer Infektionen dar. Das Procalcitonin ist ein Marker, der in der Diagnostik von Infektionen, schweren Entzündungen und Sepsis wertvolle und therapieentscheidende Aussagen ermöglicht. Er sollte allerdings nicht zum Screening asymptomatischer Personen im Rahmen arbeitsmedizinischer Vorsorgen oder sog. Manager-Untersuchungen genutzt werden, sondern lediglich beim klinischen Verdacht einer vorliegenden systemischen Infektion bei entsprechenden Symptomen.
Die Bestimmung von ACE im Serum oder Heparinplasma stellt einen wesentlichen Bestandteil der Diagnostik, Verlaufskontrolle und Therapieüberwachung von benignen Lungenerkrankungen dar. ACE ist ein Marker, der bei Sarkoidose wertvolle Aussagen zur Diagnosefindung ermöglicht. Hier zeichnet er sich durch hohe Sensitivität und Spezifität aus.
In a time when 'internationalization' and 'diversity' have become key areas universities are expected to excel in, it may seem an almost self-evident endeavor to install a memorial for a figure as influential and internationalist as Du Bois, whose connection to the Humboldt University outlasted two ideologically very different political systems. Planned to be positioned in the ground floor of the main building, the memorial, which will start production as soon as the last funding has been secured, reveals an image right at its center that "exist[s] in virtually every student's life and family album, and commonly serve[s] as vehicle[s] of recognition, remembrance and commemoration": the class photograph. What are the main considerations underlying the W. E. B. Du Bois Memorial's concept and design? How has it evolved so far? And what can such a memorial realistically achieve?
The article presents the image of Count Albert Joseph Hoditz (1706–1778) as depicted in European literature. The emphasis is not primarily on German-language literature; the study foregrounds the image of Count Hoditz in other European literatures. The investigation spans the period from the 19th century to the beginning of the 21st century.
Personalized campaign styles are of increasing importance in contemporary election campaigns at all levels of politics. Surprisingly, we know little about their implications for the behavior of successful candidates once they take public office. This paper aims to fill this gap in empirical and theoretical ways. It shows that campaign personalization results in legislative personalization. Legislators that ran personalized campaigns are found to be more likely to deviate in roll call votes and to take independent positions on the floor. These findings result from a novel dataset that matches survey evidence on candidates’ campaign styles in the 2009 German Federal Elections with the legislative behavior of successful candidates in the 17th German Bundestag (2009–2013). Combining data from the campaign and legislative arenas allows us to explore the wider consequences of campaign personalization.
In der Antike und den überlieferten antiken Mythen spielen Visionen bzw. Prophezeiungen und Träume – wie sich beispielsweise am Status des Orakels von Delphi als Omphalos (Giebel 2001, S. 7 f.) oder am vom römischen Philosophen Lukrez beschriebenen Beruf des Traumdeuters (Naf 2004, S. 90 f.) erkennen lasst – eine wichtige Rolle und nehmen ebenfalls politischen Einfluss (Trampedach 2015). Es ist daher nicht verwunderlich, dass auch gegenwärtige Mythenadaptionen, allen voran Rick Riordans Percy Jackson-Reihe bzw. mittlerweile korrekter: Reihen, in denen Percy Jackson mitunter als Crossover-Figur auftritt, auf Orakel, Prophezeiungen, Visionen und Träume vermehrt zurückgreifen...
Autor*innenfiguren finden sich seit Anbeginn der Filmgeschichte im audiovisuellen Medium - und zwar sowohl als Rekurrenz auf tatsächlich existierende historische Autor*innen als auch auf fiktive Schriftsteller*innen, die für die jeweilige Narration mitsamt der von ihnen geschriebenen Werke kreiert sind. Es bleibt eine spannende Frage, warum das audiovisuelle Medium ein so großes und langlebiges Interesse an Prozessen des Imaginierens, Schreibens und Publizierens hat, das besondere Konjunkturphasen während Herausforderungslagen des Mediums durchlebt - wie beispielsweise die jüngste Welle rund um das Millennium, die mit der zunehmenden Digitalisierung des Films zusammenfiel. Dieser Zusammenhang zwischen sich verändernden medialen Begebenheiten und dem Interesse an Autor*innenfiguren lässt sich nun auch im seriellen Erzählformat des Mediums finden. Der jüngst zu beobachtende Wandel des seriellen audio-visuellen Erzählens vollzog sich insbesondere durch das Aufkommen von Streaming-Diensten und der damit von Sendezeiten der Fernsehsender losgelösten Verfügbarkeit aller bis dato veröffentlichten Episoden einer Serie. Während zuvor ein wöchentliches Warten auf einzelne Folgen und (abgesehen vom Sonderfall der Wiederholung) nur die Verfügbarkeit dieser jeweiligen Episode gewährleistet war, besteht nun die Möglichkeit über 'Binge Watching' große Abschnitte einer Serie auf einmal anzusehen. Hierüber ergibt sich die Möglichkeit komplexe und stringent fortlaufende Handlungsstränge im seriellen Format zu erzählen. [...] Im Kontext dieser Verschachtelung von Spannungsbögen werden auch an die Darstellung von Autorschaft im seriellen Erzählformat Anforderungen gestellt, die deutlich von denen des Spielfilmformats abweichen und sich als folgende Hypothesen formulieren lassen: 1. Aufgrund ihrer Länge und der Untergliederung in einzelne Episoden mit jeweils eigenen kleinen Höhepunkten kann nicht nur die Entstehungsgeschichte eines Werks im Fokus der Narration stehen. Autor*innen im seriellen Erzählformat müssen immer wieder neue Werke angehen, sich auf immer wieder neue Art mit diesen auseinandersetzen und sich durch deren Vollendung erneut beweisen. 2. Das schöpferische Potential und der Akt der Entstehung eines Werks werden im Rahmen der Spannungsbögen getaktet. [...] 3. Als Weiterführung der letzten Konjunkturwelle im Spielfilmformat ist ein deutlich intensivierter transmedialer Umgang zu verzeichnen. [...] Wie sich diese drei Annahmen in einzelnen Beispielen manifestieren, soll anhand drei unterschiedlicher Typen von Autorenfiguren in amerikanischen Serien aufgezeigt werden.
Aufgrund wachsender Evidenz zu guten Langzeitergebnissen und geringen Komplikationsraten gewinnt die Prostataarterienembolisation (PAE) in der Therapie des Benignen Prostatasyndroms an Bedeutung. Durch ihren hohen technischen Anspruch bedarf es im Vorfeld einer umfassenden Untersuchung der Beckengefäßanatomie. Das Vorliegen eines zum Teil jungen Patientenkollektivs rückt zudem das Einsparen von Strahlung in den Fokus. In diesem Rahmen gewinnt die Magnet-Resonanz-Angiografie (MRA) an Aufmerksamkeit. Obwohl bereits erste Studien Erfolg versprechen, wird die MRA zur PAE-Planung zum Teil kritisch betrachtet, da sie aufwändiger und in der Auflösung unterlegen sei. In dieser Arbeit wurde untersucht, welche Vorteile die MRA im Zuge der PAE-Planung bietet und ob die klinische Effektivität der PAE unbeeinträchtigt bleibt. Weiterhin wurde untersucht, ob eine erfolgreiche MRA-geführte Planung die benötigte Strahlendosis reduziert.
In diese retrospektive Analyse wurden 56 Patienten, die zwischen Januar 2017 und April 2018 im Frankfurter Institut für Diagnostische und Interventionelle Radiologie eine PAE erhielten und bei denen ein vollständiger, die Interventionszeit und Strahlungsparameter umfassender Datensatz sowie eine MRA vor der PAE vorlagen, eingeschlossen. Zusätzlich wurden mittels International Prostate Symptom Score (IPSS), Quality of Life (QoL) und International Index of Erectile Function (IIEF) klinische Daten vor und nach der PAE erhoben. In der Magnet-Resonanz-Tomografie (MRT) vor der PAE wurden das Prostatavolumen, die Intravesical Prostatic Protrusion (IPP) und der Prostatic Urethral Angle (PUA) untersucht. Zur Analyse der Prostataarterie wurden Maximum Intensity Projection (MIP) und ein dreidimensionales Modell verwendet. Um die Auswirkungen einer erfolgreichen Urspungsanalyse auf Interventionszeit und Strahlungsparameter zu untersuchen, wurden diese Faktoren zwischen zwei Gruppen verglichen. In der ersten Gruppe konnte die Prostataarterie mittels MRA ermittelt werden, in der zweiten Gruppe war dies v.a. aufgrund von technischen Mängeln der Bildakquisition nicht möglich.
Der Nachweis des Ursprungs gelang bei 84,73% (111 von 131) der Prostataarterien, davon entsprangen 52,25% der A. pudenda interna, 18,92% zusammen mit der A. vesicalis superior, 13,51% seltenen Ursprüngen, 10,81% der A. obturatoria und 4,51% der vorderen Division der A. iliaca interna unterhalb der A. vesicalis inferior. Die Gruppe mit erfolgreicher Ursprungsanalyse mittels MRA zeigte signifikant geringere Werte in Fluoroskopiezeit (-26,96%, p = 0,0282), Dosisflächenprodukt (-38,04%, p = 0,0025) und Eingangsdosis (-37,10%, p = 0,0020). Die PAE bedingte eine signifikante Verbesserung in IPSS (p < 0,0001), Lebensqualität (p < 0,0001) und IIEF (p = 0,0016), dabei konnte der von den Patienten angegebene IPSS-Wert um durchschnittlich 9,42 Punkte (-43,37%) und der QoL-Wert um 2 Punkte (-50,00%) reduziert werden. Das Prostatavolumen (p < 0,0001), IPP (p = 0,0004) und PUA (p < 0,0001) zeigten sich ebenfalls signifikant reduziert. Das Volumen der Prostata schrumpfte um 4,92 ml (-8,35%), die IPP um 1,2 mm (-9,2%) und der PUA um 5,5° (-8,10%). Signifikante Zusammenhänge konnten zwischen IPSS- und QoL-Reduktion (p < 0,0001, r = 0,7555), sowie zwischen Höhe des IPSS vor der PAE und der absoluten IPSS-Reduktion (p = 0,0041, r = -0,4434) nachgewiesen werden.
Die MRA ermöglicht eine strahlungsfreie Analyse des Abgangs der Prostataarterie. Durch diese Auswertung konnte die benötigte Strahlendosis signifikant reduziert werden. Die MRA-geplante PAE erzielte eine deutliche Verbesserung der Symptomatik und der Lebensqualität. Die erektile Funktion konnte signifikant verbessert werden. Prostatavolumen, IPP und PUA zeigten zwar signifikante Veränderungen, wiesen jedoch keinen Zusammenhang zu klinischen Entwicklungen auf. Zwischen dem Ausgangsvolumen der Prostata und dem klinischen Ergebnis konnte ebenfalls keine signifikante Korrelation festgestellt werden, jedoch scheint der Ausgangswert des IPSS eine prädiktive Funktion zu haben.
Die MRA-geplante PAE ist klinisch effektiv und ermöglicht durch die Analyse der Prostataarterie eine Reduktion der benötigten Strahlung. Zusammen mit der MRT unterstützt sie die Indikationsstellung und Planung der PAE.
In higher concentrations, the blood pressure regulating hormone angiotensin II leads to vasoconstriction, hypertension, and oxidative stress by activating NADPH oxidases which are a major enzymatic source of reactive oxygen species (ROS). With the help of knockout animals, the impact of the three predominant NADPH oxidases present in the kidney, i.e., Nox1, Nox2 and Nox4 on angiotensin II-induced oxidative damage was studied. Male wildtype (WT) C57BL/6 mice, Nox1-, Nox2- and Nox4-deficient mice were equipped with osmotic minipumps, delivering either vehicle (PBS) or angiotensin II, for 28 days. Angiotensin II increased blood pressure and urinary albumin levels significantly in all treated mouse strains. In Nox1 knockout mice these increases were significantly lower than in WT, or Nox2 knockout mice. In WT mice, angiotensin II also raised systemic oxidative stress, ROS formation and DNA lesions in the kidney. A local significantly increased ROS production was also found in Nox2 and Nox4 knockout mice but not in Nox1 knockout mice who further had significantly lower systemic oxidative stress and DNA damage than WT animals. Nox2 and Nox4 knockout mice had increased basal DNA damage, concealing possible angiotensin II-induced increases. In conclusion, in the kidney, Nox1 seemed to play a role in angiotensin II-induced DNA damage.
Highlights
• PUR, PVC and PLA microplastics affect life-history parameters of Daphnia magna.
• Natural kaolin particles are less toxic than microplastics.
• Microplastic toxicity is material-specific, e.g. PVC is most toxic on reproduction.
• In case of PVC, plastic chemicals are the main driver of microplastic toxicity.
• PLA bioplastics are similarly toxic as conventional plastics.
Abstract
Given the ubiquitous presence of microplastics in aquatic environments, an evaluation of their toxicity is essential. Microplastics are a heterogeneous set of materials that differ not only in particle properties, like size and shape, but also in chemical composition, including polymers, additives and side products. Thus far, it remains unknown whether the plastic chemicals or the particle itself are the driving factor for microplastic toxicity. To address this question, we exposed Daphnia magna for 21 days to irregular polyvinyl chloride (PVC), polyurethane (PUR) and polylactic acid (PLA) microplastics as well as to natural kaolin particles in high concentrations (10, 50, 100, 500 mg/L, ≤ 59 μm) and different exposure scenarios, including microplastics and microplastics without extractable chemicals as well as the extracted and migrating chemicals alone. All three microplastic types negatively affected the life-history of D. magna. However, this toxicity depended on the endpoint and the material. While PVC had the largest effect on reproduction, PLA reduced survival most effectively. The latter indicates that bio-based and biodegradable plastics can be as toxic as their conventional counterparts. The natural particle kaolin was less toxic than microplastics when comparing numerical concentrations. Importantly, the contribution of plastic chemicals to the toxicity was also plastic type-specific. While we can attribute effects of PVC to the chemicals used in the material, effects of PUR and PLA plastics were induced by the mere particle. Our study demonstrates that plastic chemicals can drive microplastic toxicity. This highlights the importance of considering the individual chemical composition of plastics when assessing their environmental risks. Our results suggest that less studied polymer types, like PVC and PUR, as well as bioplastics are of particular toxicological relevance and should get a higher priority in ecotoxicological studies.
Geoffrey Burnstock will be remembered as the scientist who set up an entirely new field of intercellular communication, signaling via nucleotides. The signaling cascades involved in purinergic signaling include intracellular storage of nucleotides, nucleotide release, extracellular hydrolysis, and the effect of the released compounds or their hydrolysis products on target tissues via specific receptor systems. In this context ectonucleotidases play several roles. They inactivate released and physiologically active nucleotides, produce physiologically active hydrolysis products, and facilitate nucleoside recycling. This review briefly highlights the development of our knowledge of two types of enzymes involved in extracellular nucleotide hydrolysis and thus purinergic signaling, the ectonucleoside triphosphate diphosphohydrolases, and ecto-5′-nucleotidase.
The catalogue of species-group names of nine coprine genera (Coleoptera: Scarabaeidae: Scarabaeinae: Coprini), published earlier this year, is updated and revised. Presented are species-group taxa overlooked in compiling the catalogue and new species-group taxa described in 2020, i.e. after the cut-off date of the catalogue.
Presented are species-group names published in the nine coprine genera (Coleoptera: Scarabaeidae: Scarabaeinae: Coprini) having only one lateral carina on each elytron. The data include authorships, dates and pages of original descriptions, geographic distributions, and references to works pertinent to the topic.
The genus Ochodaeus in Italy: taxonomy and distribution (Coleoptera: Scarabaeoidea: Ochodaeidae)
(2020)
The author provides a taxonomic, nomenclatural and distributional review of the genus Ochodaeus Dejean, 1821 (Coleoptera: Scarabaeoidea: Ochodaeidae) in Italy. All Italian populations have been confirmed to belong to a single species, O. chrysomeloides (Schrank, 1781). After the study of a syntype, O. cychramoides Reitter, 1892, formerly considered an Italian endemic, is confirmed to be a junior synonym of O.chrysomeloides. Type material of O. chrysomeloides is believed to be destroyed, therefore a neotype is here designated and deposited at the Natural History Museum of Vienna, Austria. A lectotype is here designated for O. cychramoides and deposited in the Hungarian Natural History Museum of Budapest, Hungary. The Italian distribution of O. chrysomeloides is given in detail and illustrated by a map.
The application of natural products (NPs) as drugs and lead compounds has greatly improved human health over the past few decades. Despite their success, we still need to find new NPs that can be used as drugs to combat increasing drug resistance via new modes of action and to develop safer treatments with less side effects.
Entomopathogenic bacteria of Xenorhabdus and Photorhabdus that live in mutualistic symbiosis with nematodes are considered as promising producers of NPs, since more than 6.5% of their genomes are assigned to biosynthetic gene clusters (BGCs) responsible for production of secondary metabolites. The investigation on NPs from Xenorhabdus and Photorhabdus can not only provide new compounds for drug discovery but also help to understand the biochemical basis involved in mutualistic and pathogenic symbiosis of bacteria, nematode host and insect prey.
Nonribosomal peptides (NRPs) are a large class of NPs that are mainly found in bacteria and fungi. They are biosynthesized by nonribosomal peptide synthetases (NRPSs) and display diverse functions, representing more than 20 clinically used drugs. Although a large number of NRPs have been identified in Xenorhabdus and Photorhabdus, the advanced genome sequencing and bioinformatic analysis indicate that these bacteria still have many unknown NRPS-encoding gene clusters for NRP production that are worth to explore. Therefore, this thesis focuses on the discovery, biosynthesis, structure identification, and biological functions of new NRPs from Xenorhabdus and Photorhabdus.
The first publication describes the isolation and structure elucidation of seven new rhabdopeptide/xenortide-like peptides (RXPs) from X. innexi, incorporating putrescine or ammonia as the C-terminal amines. Bioactivity testing of these RXPs revealed potent antiprotozoal activity against the causative agents of sleeping sickness (Trypanosoma brucei rhodesiense) and malaria (Plasmodium falciparum), making them the most active RXP derivatives known to date. Biosynthetically, the initial NRPS module InxA might act iteratively with a flexible methyltransferase activity to catalyze the incorporation of the first five or six N-methylvaline/valine to these peptides.
The second publication focuses on the structure elucidation of seven unusual methionine-containing RXPs that were found as minor products in E. coli carrying the BGC kj12ABC from Xenorhabdus KJ12.1. To confirm the proposed structures from detailed HPLC-MS analysis, a solid-phase peptide synthesis (SPPS) method was developed for the synthesis of these partially methylated RXPs. These RXPs also exhibited good effects against T. brucei rhodesiense and P. falciparum, suggesting RXPs might play a role in protecting insect cadaver from soil-living protozoa to support the symbiosis with nematodes.
The third publication presents the identification of a new peptide library, named photohexapeptide library, which occurred after the biosynthetic gene phpS was activated in P. asymbiotica PB68.1 via promoter exchange. The chemical diversity of the photohexapeptides results from unusual promiscuous specificity of five out of six adenylation (A) domains being an excellent example of how to create compound libraries in nature. Furthermore, photohexapeptides enrich the family of the rare linear D-/L-peptide NPs.
The fourth publication concentrates on the structure elucidation of a new cyclohexapeptide, termed photoditritide, which was produced by P. temperata Meg1 after the biosynthetic gene pdtS was activated via promoter exchange. Photoditritide so far is the only example of a peptide from entomopathogenic bacteria that contains the uncommon amino acid homoarginine. The potent antimicrobial activity of photoditritide against Micrococcus luteus implies that photoditritide can protect the insect cadaver from food competitor bacteria in the complex life cycle of nematode and bacteria.
The last publication reports a new family of cyclic lipopeptides (CLPs), named phototemtides, which were obtained after the BGC pttABC from P. temperata Meg1 was heterologously expressed in E. coli. The gene pttA encodes an MbtH protein that was required for the biosynthesis of phototemtides in E. coli. To determine the absolute configurations of the hydroxy fatty acids, a total synthesis of the major compound phototemtide A was performed. Although the antimalarial activity of phototemtide A is only weak, it might be a starting point towards a selective P. falciparum compound, as it shows no activity against any other tested organisms.
Cisplatin, which induces DNA damage, is standard chemotherapy for advanced bladder cancer (BCa). However, efficacy is limited due to resistance development. Since artesunate (ART), a derivative of artemisinin originating from Traditional Chinese Medicine, has been shown to exhibit anti-tumor activity, and to inhibit DNA damage repair, the impact of artesunate on cisplatin-resistant BCa was evaluated. Cisplatin-sensitive (parental) and cisplatin-resistant BCa cells, RT4, RT112, T24, and TCCSup, were treated with ART (1–100 µM). Cell growth, proliferation, and cell cycle phases were investigated, as were apoptosis, necrosis, ferroptosis, autophagy, metabolic activity, and protein expression. Exposure to ART induced a time- and dose-dependent significant inhibition of tumor cell growth and proliferation of parental and cisplatin-resistant BCa cells. This inhibition was accompanied by a G0/G1 phase arrest and modulation of cell cycle regulating proteins. ART induced apoptos is by enhancing DNA damage, especially in the resistant cells. ART did not induce ferroptosis, but led to a disturbance of mitochondrial respiration and ATP generation. This impairment correlated with autophagy accompanied by a decrease in LC3B-I and an increase in LC3B-II. Since ART significantly inhibits proliferative and metabolic aspects of cisplatin-sensitive and cisplatin-resistant BCa cells, it may hold potential in treating advanced and therapy-resistant BCa.
Over the last decade, cryo-EM has developed exponentially due to improvements in both hardware (“machine”-based) and software (“algorithm”-based). These improvements have pushed the best achievable resolutions closer to atomic level, bridging “gaps” not covered by other biophysical techniques, and allowing more difficult biological questions to be addressed. Thus, this PhD project was designed and constructed to apply cryo-EM to answer biological questions, while allowing simultaneous cryo-EM method development.
The biological focus of this research is pentameric ligand-gated ion channels (pLGICs), specifically the serotonin receptor type-3 receptor (5HT3R), which also belongs to the Cys-loop receptor family. 5HT3R plays an important role in fast synaptic signal transduction in response to agonist and antagonist binding. Binding to its native ligand results in opening of the channel at the transmembrane domain, allowing cations to pass through, resulting in membrane depolarization and conversion of the chemical signal into an electrical one.
This work consisted mainly of two specific aims. One was focused on conformational investigation of 5HT3R in its ligand-bound open conformation, using cryo-electron microscopy (cryo-SPA), in order to understand the gating mechanism upon ligand activation. The other one was to combine SPA with cryo-ET and STA to push the resolution limitation of conventional cryo-ET and STA workflows.
In the end, three different cryo-EM conformations of membrane-embedded 5HT3R were resolved using cryo-SPA, two structures in resting closed forms, one C5-symmetric and one C1-asymmetric, and one serotonin-bound open form. These three structures presented a number of novel features related to the transition of the receptor to its ion-conductive state. Specifically, the serotonin-bound receptor shows asymmetric opening, which was speculated to occur via an intermediate asymmetric Apo state. In addition to the cryo-SPA work, application of cryo-ET and STA to the study of 5HT3R in native vesicles is described in this thesis. Additional work on methods development, focused on combining SPA and STA techniques, along with preliminary results on tobacco mosaic virus are also detailed and discussed.
Moreover, previously unreported asymmetric arrangements of the subunits of the homopentameric 5HT3R around the pore axis were revealed. The asymmetric open state is stabilized by phospholipids inserted at the interface between subunits, at a site well-documented for the binding of allosteric pLGIC modulators. These results not only give structural support to a large body of functional data on the effects of lipids on the function of this receptor family, but also provide structural guidance for future studies in this field. Meanwhile, the SPA-STA combined methods developed during the course of this work have the potential to help resolve higher resolution tomography-based structures, which would benefit researchers seeking to do in-situ-based structural studies.
Characterization of a dual BET/HDAC inhibitor for treatment of pancreatic ductal adenocarcinoma
(2020)
Pancreatic ductal adenocarcinoma (PDAC) is resistant to virtually all chemo‐ and targeted therapeutic approaches. Epigenetic regulators represent a novel class of drug targets. Among them, BET and HDAC proteins are central regulators of chromatin structure and transcription, and preclinical evidence suggests effectiveness of combined BET and HDAC inhibition in PDAC. Here, we describe that TW9, a newly generated adduct of the BET inhibitor (+)‐JQ1 and class I HDAC inhibitor CI994, is a potent dual inhibitor simultaneously targeting BET and HDAC proteins. TW9 has a similar affinity to BRD4 bromodomains as (+)‐JQ1 and shares a conserved binding mode, but is significantly more active in inhibiting HDAC1 compared to the parental HDAC inhibitor CI994. TW9 was more potent in inhibiting tumor cell proliferation compared to (+)‐JQ1, CI994 alone or combined treatment of both inhibitors. Sequential administration of gemcitabine and TW9 showed additional synergistic antitumor effects. Microarray analysis revealed that dysregulation of a FOSL1‐directed transcriptional program contributed to the antitumor effects of TW9. Our results demonstrate the potential of a dual chromatin‐targeting strategy in the treatment of PDAC and provide a rationale for further development of multitarget inhibitors.
Introduction: Esophageal atresia with or without tracheoesophageal fistula (EA/TEF) occurs approximately 1 in 3.500 live births representing the most common malformation of the upper digestive tract. Only half a century ago, EA/TEF was fatal among affected newborns suggesting that the steady birth prevalence might in parts be due to mutational de novo events in genes involved in foregut development.
Methods: To identify mutational de novo events in EA/TEF patients, we surveyed the exome of 30 case-parent trios. Identified and confirmed de novo variants were prioritized using in silico prediction tools. To investigate the embryonic role of genes harboring prioritized de novo variants we performed targeted analysis of mouse transcriptome data of esophageal tissue obtained at the embryonic day (E) E8.5, E12.5, and postnatal.
Results: In total we prioritized 14 novel de novo variants in 14 different genes (APOL2, EEF1D, CHD7, FANCB, GGT6, KIAA0556, NFX1, NPR2, PIGC, SLC5A2, TANC2, TRPS1, UBA3, and ZFHX3) and eight rare de novo variants in eight additional genes (CELSR1, CLP1, GPR133, HPS3, MTA3, PLEC, STAB1, and PPIP5K2). Through personal communication during the project, we identified an additional EA/TEF case-parent trio with a rare de novo variant in ZFHX3. In silico prediction analysis of the identified variants and comparative analysis of mouse transcriptome data of esophageal tissue obtained at E8.5, E12.5, and postnatal prioritized CHD7, TRPS1, and ZFHX3 as EA/TEF candidate genes. Re-sequencing of ZFHX3 in additional 192 EA/TEF patients did not identify further putative EA/TEF-associated variants.
Conclusion: Our study suggests that rare mutational de novo events in genes involved in foregut development contribute to the development of EA/TEF.
Type-II multiferroic materials, in which ferroelectric polarization is induced by inversion non-symmetric magnetic order, promise new and highly efficient multifunctional applications based on mutual control of magnetic and electric properties. However, to date this phenomenon is limited to low temperatures. Here we report giant pressure-dependence of the multiferroic critical temperature in CuBr2: at 4.5 GPa it is enhanced from 73.5 to 162 K, to our knowledge the highest TC ever reported for non-oxide type-II multiferroics. This growth shows no sign of saturating and the dielectric loss remains small under these high pressures. We establish the structure under pressure and demonstrate a 60\% increase in the two-magnon Raman energy scale up to 3.6 GPa. First-principles structural and magnetic energy calculations provide a quantitative explanation in terms of dramatically pressure-enhanced interactions between CuBr2 chains. These large, pressure-tuned magnetic interactions motivate structural control in cuprous halides as a route to applied high-temperature multiferroicity.
Inflammation is a highly regulated biological response of the immune system that is triggered by assaulting pathogens or endogenous alarmins. It is now well established that some soluble extracellular matrix constituents, such as small leucine-rich proteoglycans (SLRPs), can act as danger signals and trigger aseptic inflammation by interacting with innate immune receptors. SLRP inflammatory signaling cascade goes far beyond its canonical function. By choosing specific innate immune receptors, coreceptors, and adaptor molecules, SLRPs promote a switch between pro- and anti-inflammatory signaling, thereby determining disease resolution or chronification. Moreover, by orchestrating signaling through various receptors, SLRPs fine-tune inflammation and, despite their structural homology, regulate inflammatory processes in a molecule-specific manner. Hence, the overarching theme of this review is to highlight the molecular and functional specificity of biglycan-, decorin-, lumican-, and fibromodulin-mediated signaling in inflammatory and autoimmune diseases.
Aim: Left ventricular non-compaction (LVNC) is perceived as a rare high-risk cardiomyopathy characterized by excess left ventricular (LV) trabeculation. However, there is increasing evidence contesting the clinical significance of LV hyper-trabeculation and the existence of LVNC as a distinct cardiomyopathy. The aim of this study is to assess the association of LV trabeculation extent with cardiovascular morbidity and all-cause mortality in patients undergoing clinical cardiac magnetic resonance (CMR) scans across 57 European centers from the EuroCMR registry.
Methods and Results: We studied 822 randomly selected cases from the EuroCMR registry. Image acquisition was according to international guidelines. We manually segmented images for LV chamber quantification and measurement of LV trabeculation (as per Petersen criteria). We report the association between LV trabeculation extent and important cardiovascular morbidities (stroke, atrial fibrillation, heart failure) and all-cause mortality prospectively recorded over 404 ± 82 days of follow-up. Maximal non-compaction to compaction ratio (NC/C) was mean (standard deviation) 1.81 ± 0.67, from these, 17% were above the threshold for hyper-trabeculation (NC/C > 2.3). LV trabeculation extent was not associated with increased risk of the defined outcomes (morbidities, mortality, LV CMR indices) in the whole cohort, or in sub-analyses of individuals without ischaemic heart disease, or those with NC/C > 2.3.
Conclusion: Among 882 patients undergoing clinical CMR, excess LV trabeculation was not associated with a range of important cardiovascular morbidities or all-cause mortality over ~12 months of prospective follow-up. These findings suggest that LV hyper-trabeculation alone is not an indicator for worse cardiovascular prognosis.
The RNA cleaving catalyst tris(2-aminobenzimidazole) when attached to the 5’ terminus of oligonucleotides cuts complementary RNA strands in a highly site-specific manner. Conjugation was previously achieved by the acylation of an amino linker by an active ester of the catalyst. However, this procedure was low yielding and not reliable. Here, a phosphoramidite building block is described that can be coupled to oligonucleotides by manual solid phase synthesis in total yields around 85%. Based on this chemistry, we have now studied the impact of LNA (locked nucleic acids) nucleotides on the rates and the site-specificities of RNA cleaving conjugates. The highest reaction rates and the most precise cuts can be expected when the catalyst is attached to a strong 5’ closing base pair and when the oligonucleotide contains several LNA units that are equally distributed in the strand. However, when placed in the 5’ position, LNA building blocks tend to diminish the specificity of RNA cleavage.
The opportunistic human pathogen Acinetobacter baumannii is one of the leading causes of nosocomial infections. The high prevalence of multidrug‐resistant strains, a high adaptability to changing environments and an overall pronounced stress resistance contribute to persistence and spread of the bacteria in hospitals and thereby promote repeated outbreaks. Altogether, the success of A. baumannii is mainly built on adaptation and stress resistance mechanisms, rather than relying on ‘true’ virulence factors. One of the stress factors that pathogens must cope with is osmolarity, which can differ between the external environment and different body parts of the human host. A. baumannii ATCC 19606T accumulates the compatible solutes glutamate, mannitol and trehalose in response to high salinities. In this work, it was found that most of the solutes vanish immediately after reaching stationary phase, a very unusual phenomenon. While glutamate can be metabolized, mannitol produced by MtlD is excreted to the medium in high amounts. First results indicate that A. baumannii ATCC 19606T undergoes a rapid switch to a dormant state (viable but non‐culturable) after disappearance of the compatible solutes. Resuscitation from this state could easily be achieved in PBS or fresh medium.
Employing an intersectional approach—drawing on cultural and new kinship studies, (medical) anthropology, gender and media studies—this article analyzes how the 2013 MTV series Generation Cryo as cultural text deals with medicalized masculinities and (in)fertilities. It asks in what ways masculinities and also fathers, fathering, and fatherhoods are (re)presented and negotiated in a story which has sperm donation by an anonymous donor and the donor siblings and/in their respective families at its center. In the show, essentially an (auto)biographical narrative, all families emphasize social parenthood over genetic inheritance, yet there are also deep-seated insecurities (re)triggered by the donor who is literally and metaphorically a present absence transforming into a potential family member, thus shaking family tectonics and challenging familial/familiar gender and family roles. Generation Cryo is a story about donor conceived children, but also about clinically infertile men and their social roles as fathers, their struggles to narrate and embody individual forms of masculinities in the face of cultural normative templates of hegemonic masculinities— complex practices constantly oscillating between genetic essentialism and social parenthood.
Wer waren die Literaturwissenschaftler, die bei der Gründung 1914 an die Universität Frankfurt am Main berufen wurden, die das akademische Leben der Stadt Frankfurt in der Weimarer Republik mitprägten, die nach 1933 in Frankfurt weiterhin Literaturwissenschaft betrieben oder die vertrieben wurden? Ein zweisemestriges interdisziplinäres Lehrforschungsseminar am Fachbereich 10 (Neuere Philologien) hat anlässlich des Jubiläums zum 100-jährigen Bestehen der Universität im Jahr 2014 Antworten auf diese Fragen gesucht. Das Ergebnis ist eine virtuelle Ausstellung mit 20 Porträts (Goethe Universität Frankfurt am Main, 2017). Diese Ausstellung war jedoch nur ein Teil einer Reihe von Veranstaltungen, die sich im Jubiläumsjahr der Frankfurter Universität mit den Literaturwissenschaften in Frankfurt befassten.
Signal transduction and the regulation of gene expression are fundamental processes in every cell. RNA-binding proteins (RBPs) play a key role in the post-transcriptional modulation of gene expression in response to both internal and external stimuli. However, how signaling pathways regulate the assembly of RBPs with mRNAs remains largely unknown. Here, we summarize observations showing that the formation and composition of messenger ribonucleoprotein particles (mRNPs) is dynamically remodeled in space and time by specific signaling cascades and the resulting post-translational modifications. The integration of signaling events with gene expression is key to the rapid adaptation of cells to environmental changes and stress. Only a combined approach analyzing the signal transduction pathways and the changes in post-transcriptional gene expression they cause will unravel the mechanisms coordinating these important cellular processes.
The Iranian species of the genus Anomalon Panzer, 1804 (Hymenoptera: Ichneumonidae: Anomaloninae) are reviewed. Four species, Anomalon amseli (Hedwig, 1961), A. chinense (Kokujev, 1915), A. cruentatum (Geoffroy, 1785) and A. narinae Zardouei & Rakhshani sp. nov., are found to occur in Iran. The female of A. amseli is described for the first time. Anomalon chinense is a new record for Iran. A key to the known Anomalon species of Iran is provided.
Der Beitrag unternimmt einen Vergleich zweier Romane, die inhaltlich, erzähltechnisch und sprachlich eng miteinander verknüpft sind, obwohl ihre Entstehungszeiten etwa 50 Jahre auseinander liegen: Juan Rulfos "Pedro Páramo" und Yuri Herreras "Señales que precederán al fin del mundo". Beide Autoren lassen ihre Figuren aus einem Nicht-Ort oder einem "unsichtbaren Ort" (was die wörtliche Übersetzung von 'Hades' wäre) sprechen, aus dem Paradox des "Ich-bin-tot"-Sagens, und verweisen damit auf altmexikanische, altgriechische sowie mittelalterliche Unterweltreisen. Diese zeichnen sich dadurch aus, dass von dort niemand zurückkehren kann, dennoch ist es einigen mythologische Figuren gelungen, die Grenze zwischen Leben und Tod gewissermaßen kurzzeitig außer Kraft zu setzen: Orpheus, Odysseus, Herakles, Aeneas, Dante, bei den Mayas sind es Junajpu und Xbalanq'e, die im Ballspiel die Herren Xibalbas, der Unterwelt der Maya, besiegen, um nur einige Beispiele zu nennen. Die eigentlich unerlaubte Wiederkehr bzw. Rückkehr hängt eng mit der Schau einer Vergangenheit zusammen, die zentral ist für ein Verständnis der regionalen/nationalen Gegenwart. Den Romanen Rulfos und Herreras ist eine inszenierte Abwärtsbewegung gemeinsam, der schrittweise Abstieg in eine politische Vergangenheit, die die Gegenwart der Protagonist*innen verstehen helfen soll. Beide Romane verbinden damit auch eine Suche nach einem abwesenden Familienmitglied. Zudem greift Herrera auf die besondere Erzählweise Rulfos zurück, die sich erst aus einem Sprechen aus dem Tod ergeben kann.
A new fossil diatom species, Tertiarius minutulus sp. nov., is described from a sediment sequence DEEP-5045-1 of Lake Ohrid. The species is characterized by small valves (3.0–8.0 μm) with a round shape, a marginal area with radially arranged costae and a central uneven area with scattered areolae. Externally, the alveoli are occluded by cribra perforated by irregularly arranged pores. Internally, the alveoli are simple and areolae are occluded with domed cribra. The marginal fultoportulae are situated on costae close to the valve margin, located on every 5th or 7th thick internal costa. One to three fultoportulae are present on the valve face, each surrounded by two to three satellite pores. One rimoportula is present, positioned on a costa at the valve face / mantle junction. The species is compared with morphologically similar taxa and a detailed differential diagnosis is provided. Tertiarius minutulus sp. nov. is known only as a fossil taxon from Lake Ohrid, with a first occurrence during the early stages of lake basin development.
Diese Thesis befasst sich mit dem Problem korrelierter Elektronensysteme in realen Materialien. Ausgangspunkt hierbei ist die quantenmechanische Beschreibung dieser Systeme im Rahmen der sogenannten Kohn-Scham Dichtefunktionaltheorie, welche die Elektronen der Kristallsysteme als effektiv nicht-wechselwirkende Teilchen beschreibt.
Während diese Modellierung im Falle vieler Materialklassen erfolgreich ist, unterscheiden sich die korrelierten Elektronensysteme dadurch, dass der kollektive Charakter der Elektronendynamik nicht zu vernachlässigen ist.
Um diese Korrelationseffekte genauer zu untersuchen, verwenden wir in dieser Arbeit das Hubbard-Modell, welches mit der projektiven Wannierfunktionsmethode aus der Kohn-Scham Dichtefunktionaltheorie konstruiert werden kann.
Das Hubbard-Modell umfasst hierbei nur die lokale Elektron-Elektron-Wechselwirkung auf einem Gitter. Auch wenn das Modell augenscheinlich sehr simpel ist, existieren exakte Lösungen nur in bestimmten Grenzfällen. Dies macht die Entwicklung approximativer Ansätze erforderlich, wobei die Weiterentwicklung der sogenannten Two-Particle Self-Consistent Methode (TPSC) eine zentrale Rolle dieser Arbeit einnimmt.
Bei TPSC handelt es sich um eine Vielteilchenmethode, die in der Sprache funktionaler Ableitungen und sogenannter conserving approximations hergeleitet werden kann.
Der zentrale Gedanke dabei ist, den effektiven Wechselwirkungsvertex als statisch und lokal zu approximieren. Dies wiederum erlaubt die Bewegungsgleichung des Systems
erheblich zu vereinfachen, sodass eine numerische approximative Lösung des Hubbard-Modells möglich wird. Vorsetzung hierbei ist nur, dass sich das System in der normalleitenden Phase befindet und die bei Phasenübergängen entstehenden Fluktuationen nicht zu groß sind.
Während diese Methode ursprünglich von Y. M. Vilk und A.-M. Tremblay für das Ein-Orbital Hubbard-Modell entwickelt wurde, stellen wir in dieser Arbeit eine Erweiterung auf Viel-Orbital-Systeme vor.
Im Falle mehrerer Orbitale treten in der TPSC-Herleitung einzelne Komplikationen auf, die mit weiteren Approximationen behandelt werden müssen. Diese werden anhand eines einfachen Zwei-Orbital Modell-Systems diskutiert und die TPSC-Ergebnisse werden darüber hinaus mit den Ergebnissen der etablierten dynamischen Molekularfeldnährung verglichen.
In diesem Zusammenhang werden auch mögliche zukünftige Erweiterungen bzw. Verbesserungen von TPSC diskutiert.
Ein weiterer wichtiger Aspekt ist die Anwendung von TPSC auf reale Materialien.
In diesem Zusammenhang werden in dieser Arbeit die supraleitenden Eigenschaften der organischen K-(ET)2X Systeme untersucht. Hierbei lassen die TPSC-Resultate darauf schließen, dass das populäre Dimer-Modell, welches zur Beschreibung dieser Materialien herangezogen wird, nicht genügt um die experimentell bestimmten kritischen Temperaturen zu erklären und dass das komplexere Molekülmodell weitere exotische supraleitende Lösungen zulässt.
Schließlich untersuchen wir außerdem die elektronischen Eigenschaften des eisenbasierten Supraleiters LiFeAs und diskutieren inwieweit nicht-lokale Korrelationseffekte, welche durch TPSC aufgelöst werden können, die experimentellen Daten reproduzieren.
The taxonomic and faunistic status of the spider family Oecobiidae in Iran, Afghanistan and Turkmenistan is revised. A new species, namely Uroctea gambronica sp. nov. (♂) is described from southern Iran, and the male of U. grossa Roewer, 1960 is described and illustrated for the first time. Additionally, new faunistic data are provided, including the first records of Oecobius putus O. Pickard-Cambridge, 1876 and U. grossa in Afghanistan and Turkmenistan, respectively, and the re-evaluation of previously misidentified and questionable records of this family in the region. The known distribution ranges of all species are mapped for these three countries.
Ein halbes Jahrhundert Judaistik in Frankfurt : das »kleine Fach« feiert 50-jähriges Bestehen
(2020)
Kein gemeinsames Mittagessen im Dasein, kein Kinobesuch in der Pupille – und der letzte Kaffee im Hopplo ist auch schon eine Weile her. Spätestens im März war klar: Das Sommersemester 2020 wird anders. Corona geht herum, und wir bleiben zu Hause. Nachdem der Semesterstart auf den 20. April verschoben wurde, startete die Universität erstmals mit einem reinen Online-Angebot. Doch was bedeutet Studieren in Zeit der Pandemie? Und wie kommen die Studis mit dieser ungewohnten Situation zurecht?
The genome of the halophilic archaeon Haloferax volcanii encodes more than 40 one-domain zinc finger µ-proteins. Only one of these, HVO_2753, contains four C(P)XCG motifs, suggesting the presence of two zinc binding pockets (ZBPs). Homologs of HVO_2753 are widespread in many euryarchaeota. An in frame deletion mutant of HVO_2753 grew indistinguishably from the wild-type in several media, but had a severe defect in swarming and in biofilm formation. For further analyses, the protein was produced homologously as well as heterologously in Escherichia coli. HVO_2753 was stable and folded in low salt, in contrast to many other haloarchaeal proteins. Only haloarchaeal HVO_2753 homologs carry a very hydrophilic N terminus, and NMR analysis showed that this region is very flexible and not part of the core structure. Surprisingly, both NMR analysis and a fluorimetric assay revealed that HVO_2753 binds only one zinc ion, despite the presence of two ZBPs. Notably, the analysis of cysteine to alanine mutant proteins by NMR as well by in vivo complementation revealed that all four C(P)XCG motifs are essential for folding and function. The NMR solution structure of the major conformation of HVO_2753 was solved. Unexpectedly, it was revealed that ZBP1 was comprised of C(P)XCG motifs 1 and 3, and ZBP2 was comprised of C(P)XCG motifs 2 and 4. There are several indications that ZBP2 is occupied by zinc, in contrast to ZBP1. To our knowledge, this study represents the first in-depth analysis of a zinc finger µ-protein in all three domains of life.
Almanya Federal Cumhuriyeti'nde görev yapan Türkçe ve Türk Kültürü Dersi öğretmenlerine yönelik 2020 Mayıs- Haziran aylarında toplam 69 çevrimiçi seminer düzenlenmiştir. Seminerlere Almanya Federal Cumhuriyeti’nde görev yapan MEB Türkçe ve Türk Kültürü Dersi öğretmenleri katılmış; her bir seminerden sonra öğretmen görüşleri alınmıştır. Araştırmanın evrenini 2019-2020 eğitim öğretim yılı itibarı ile Almanya'da görevli 1338 Türkçe öğretmeni, örneklem grubunu ise MEB tarafından görevlendirilen 506 Türkçe ve Türk Kültürü dersi öğretmeni oluşturmaktadır. Araştırmacı grubu tarafından geliştirilen veri toplama anketi Mayıs -Haziran 2020 aylarında (pandemi dönemi) verilen çevrimiçi seminerlere paralel olarak uygulanmıştır. Bu çalışmada öğretmenlerin yurt dışındaki öğretmenlere verilen seminerler belli bir farkındalığın oluşmasını sağlamış; yurt dışı teşkilatının öğrenen organizasyonlar olarak öğretmenlerin bu tür programlara ilgi düzeyleri, varlığı/yokluğu, katılım sayısı ve sıklığı ile ölçümlenerek değerlendirilmiştir. Elde edilen bulgular, bu tür seminer çalışmalarının gelecek dönemlerde de yapılmasının elzem olduğunu ortaya koymuştur.
Central cholinergic function and metabolic changes in streptozotocin‐induced rat brain injury
(2020)
As glucose hypometabolism in the brain is an early sign of Alzheimer´s dementia (AD), the diabetogenic drug streptozotocin (STZ) has been used to induce Alzheimer‐like pathology in rat brain by intracereboventricular injection (icv‐STZ). However, many details of the pathological mechanism of STZ in this AD model remain unclear. Here, we report metabolic and cholinergic effects of icv‐STZ using microdialysis in freely moving animals. We found that icv‐STZ at a dose of 3 mg/kg (2 × 1.5 mg/kg) causes overt toxicity reflected in body weight loss. Three weeks after STZ administration, histological examination revealed a high number of glial fibrillary acidic protein reactive cells in the hippocampus, accompanied by Fluoro‐Jade C‐positive cells in the CA1 region. Glucose and lactate levels in microdialysates were unchanged, but mitochondrial respiration measured ex vivo was reduced by 9%–15%. High‐affinity choline uptake, choline acetyltransferase, and acetylcholine esterase (AChE) activities in the hippocampus were reduced by 16%, 28%, and 30%, respectively. Importantly, extracellular acetylcholine (ACh) levels in the hippocampus were unchanged and responded to behavioral and pharmacological challenges. In comparison, extracellular ACh levels and cholinergic parameters in the striatum were unchanged or slightly increased. We conclude that the icv‐STZ model poorly reflects central cholinergic dysfunction, an important characteristic of dementia. The icv‐STZ model may be more aptly described as an animal model of hippocampal gliosis.
Alzheimer’s disease (AD) is the major cause of dementia. It is characterized by the accumulation of abnormal proteins (amyloid-β plaque and neurofibrillary tangles) leading to loss of synapses, dendrites, neurons, memory and cognition. Sporadic late-onset AD is the major type of AD characterized by unclear etiology and a lack of disease-modifying therapy. To understand this disease, an alternative AD hypothesis has been proposed: AD may resemble diabetes in the brain or “diabetes type 3”. This hypothesis is supported by the fact that (1) brain glucose hypometabolism precedes AD clinical symptoms and (2) diabetes increases the risk of AD. To test this hypothesis, wild-type rats receiving intracerebroventricular administration of streptozotocin (icv-STZ) were used as a model. Streptozotocin (STZ) is a glucosamine-nitrosourea compound commonly used to induce experimental diabetes by peripheral administration. A similar pathological mechanism to peripheral STZ is then proposed to explain icv-STZ toxicity: insulin receptor signaling impairment results in glucose hypometabolism leading to cognitive deficits.
Objective: Icv-STZ model seems promising as a toxin-induced, non-transgenic AD model with the possibility to connect AD and diabetes mellitus (DM), one of the risk factors for AD. However, the mechanisms of how icv-STZ induced AD-like symptoms are unclear. Therefore, using microdialysis as the main technique, we tested 2 AD hypotheses in this model: (1) the glucose hypometabolism as an alternative AD hypothesis and (2) the cholinergic deficit as an important characteristic of AD pathology. Hippocampus was chosen because cholinergic function in this region is severely affected in AD. In comparison, the striatum was chosen because it contains cholinergic interneurons and is less affected in AD.
Methods: In this study, we used male Wistar rats of 190-220 g body weight (5 weeks of age). The rats were injected intracerebrally with STZ at a dose of 3 mg/kg (2x1.5 mg/kg; „high dose“) and 0.6 mg/kg („low dose“) with saline as control. After 21 days, samples were collected to investigate cholinergic and metabolic changes using histology, biochemistry, and neurochemistry. Brain injury was confirmed using GFAP staining and Fluoro jade staining in the hippocampus. Mitochondrial toxicity was investigated by measurement of mitochondrial
respiratory function in both hippocampus and striatum. Cholinergic markers such as acetylcholinesterase (AChE) activity, choline acetyltransferase (ChAT) activity, and choline transporter (CHT-1) activity, commonly known as high-affinity choline uptake (HACU), were measured in both hippocampus and striatum using a spectrophotometer and a scintillator.
Microdialysis is the main technique in our study. It was done in awake animals under behavioral or pharmacological stimulation. We used a self-built probe with a semi-permeable membrane (pore size of 30 kDa) that was implanted in either hippocampus or striatum. The probes were then perfused with artificial cerebrospinal fluid (aCSF) supplemented with 0.1 μM neostigmine for extracellular acetylcholine level measurement. During the perfusion, small hydrophilic compounds from brain extracellular space diffuse into the dialysates. Dialysates of 15 minutes intervals were collected for 90 minutes and used for analysis. After collection of dialysates for the first 90 minutes (basal data), rats were moved to an open field box (35x32x20 cm) for behavioral stimulation. After collection of the second 90 minute dialysates, the rats were transferred back to the microdialysis cage and dialysates were collected for another 90 minutes. On day 2, after collection of dialysates under basal conditions, 1 μM scopolamine was added to the perfusion solution for stimulation of acetylcholine release. The dialysates were also collected for 90 min followed by another 90 min of dialysis without scopolamine. The microdialysate samples were then analyzed as follows. ACh level was measured by HPLC-ECD. Glucose metabolites (glucose, lactate, pyruvate) were measured by a CMA-600 microanalyzer. An alternative energy metabolite (beta-hydroxybutyrate/BHB) was measured by GC-MS. Choline and glycerol as membrane breakdown markers were also measured by HPLC-ECD and CMA-600 microanalyzer, respectively. Markers of oxidative stress (isoprostanes) were measured using a commercially available ELISA kit.
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Currently, the genus Polypedates comprises 26 species distributed in South, Southeast, and East Asia. Because of their relatively low dispersal capability and intolerance to seawater, this genus is ideal for the study of terrestrial range evolution that extends into the island archipelagos of southeastern Asia. In this study, based on data compiled for Polypedates from previous studies and partial mitochondrial and nuclear genes collected in this study, we performed systematic biogeographical analysis. We confirmed a Sundaland origin for the extant genus and showed northward dispersal into mainland Southeast Asia and Asia, which coincided with the timing of paleoclimatic change from the Oligocene to Middle Miocene. Climate fluctuations had a profound impact on species diversification within the genus Polypedates. Furthermore, the Red River did not mediate species exchange between Southeast Asia and mainland Asia until the end of the Miocene, with the sudden onset of northward dispersal in several clades independently at that time. Alternatively, the lineage of widespread insular P. leucomystax strongly supports the hypothesis of terrestrial connection between island archipelagos of Southeast Asia during the Mid-Pleistocene paleoclimate fluctuations. Our biogeographical analysis also supports the recent introduction of P. leucomystax to the Philippines and Ryukyus, as previously suggested.
Currently, due to the misuse of antibiotics, we are facing a major public health problem. The resistance to antibiotics of certain bacterial strains makes the treatment of infections very complex.
In this context, the present thesis project concerns the study of a bacterial efflux complex capable of transporting antibiotics from the cytoplasm to the outside of the cell. This complex is composed of an inner-membrane Major Facilitator Superfamily (MFS) transporter (EmrB, E. coli multidrug resistance), a channel of the outer membrane TolC (Tolerance to Colicin E1) and a periplasmic adapter (EmrA, E. coli multidrug resistance). Unlike RND-type efflux systems (such as AcrAB-TolC), little is known about the MFS-type EmrAB-TolC system. It is therefore important to study the entire complex on a structural and functional level, to analyse the marked differences between these two types of transport systems. The goal of my thesis project was to study at least one EmrAB-TolC complex from a structural point of view. For my studies the aim was to isolate the complex directly from bacteria overexpressing the three protein partners. In a first step, 15 homologous EmrAB-TolC systems were identified and their corresponding genes amplified from genomic DNA of different Gram-negative bacteria. Among the genes of the 15 systems, the genes coding for the E. coli and V. cholerae systems were further studied. The expression vectors encoded fluorescent markers for the monitoring of the expression levels of different proteins and for studying the formation of complexes. In a first step, the different protein expression levels (EmrB-mRFP1 and EmrA-sfGFP) were studied for several expression strains of E. coli by measuring the red and green fluorescence levels and by Western blot (anti-His, Myc, and Strep for EmrB, EmrA, and TolC). The E. coli strain C41(DE3) was best suited for co-expression of EmrAB-TolC. In a second step, the FSEC (Fluorescence detection Size Exclusion Chromatography) methodology was used to identify a complex suitable for structural study. Thus this method enabled the observation that the EmrAB-TolC complex of E. coli was produced in higher amount than that of V. cholerae. The final co-purification protocol consists in perfoming a gentle lysis of the bacteria using lysozyme, then after solubilization with DDM, the purification is started by a Ni2+-NTA affinity chromatography step followed by a size exclusion chromatography step. Finally, the fractions containing the three protein partners are used for the detergent-exchange by amphipol A8-35 before the structural study by electron microscopy. Negative stain EM-micrographs displayed elongated objects with a length of 33 nm in side view. An average image of EmrAB-TolC shows similarities to that of the AcrAB-TolC complex observed under similar conditions. Similarities included the characteristic densities of TolC. Whereas differences were found in the lower part of EmrAB which is thinner than the lower part of AcrAB. The densities visible above the amphipol-ring correspond to EmrA, which displays a channel-like structure as in AcrA. The channel however seems to extend further towards the amphipol belt. Since EmrB does not have an extended periplasmic domain as the RND proteins have, these densities are therefore solely assigned to EmrA. EmrA, on the other side, contacts TolC akin to the interaction of AcrA/MexA to their cognate outer membrane channels (TolC/OprM) in a ‘tip-to-tip’ fashion.
Autism spectrum disorders (ASD) are highly heritable and are characterized by deficits in social communication and restricted and repetitive behaviors. Twin studies on phenotypic subdomains suggest a differing underlying genetic etiology. Studying genetic variation explaining phenotypic variance will help to identify specific underlying pathomechanisms. We investigated the effect of common variation on ASD subdomains in two cohorts including >2500 individuals. Based on the Autism Diagnostic Interview-Revised (ADI-R), we identified and confirmed six subdomains with a SNP-based genetic heritability h2SNP = 0.2–0.4. The subdomains nonverbal communication (NVC), social interaction (SI), and peer interaction (PI) shared genetic risk factors, while the subdomains of repetitive sensory-motor behavior (RB) and restricted interests (RI) were genetically independent of each other. The polygenic risk score (PRS) for ASD as categorical diagnosis explained 2.3–3.3% of the variance of SI, joint attention (JA), and PI, 4.5% for RI, 1.2% of RB, but only 0.7% of NVC. We report eight genome-wide significant hits—partially replicating previous findings—and 292 known and novel candidate genes. The underlying biological mechanisms were related to neuronal transmission and development. At the SNP and gene level, all subdomains showed overlap, with the exception of RB. However, no overlap was observed at the functional level. In summary, the ADI-R algorithm-derived subdomains related to social communication show a shared genetic etiology in contrast to restricted and repetitive behaviors. The ASD-specific PRS overlapped only partially, suggesting an additional role of specific common variation in shaping the phenotypic expression of ASD subdomains.
One current goal in native mass spectrometry is the assignment of binding affinities to noncovalent complexes. Here we introduce a novel implementation of the existing laser-induced liquid bead ion desorption (LILBID) mass spectrometry method: this new method, LILBID laser dissociation curves, assesses binding strengths quantitatively. In all LILBID applications, aqueous sample droplets are irradiated by 3 µm laser pulses. Variation of the laser energy transferred to the droplet during desorption affects the degree of complex dissociation. In LILBID laser dissociation curves, laser energy transfer is purposely varied, and a binding affinity is calculated from the resulting complex dissociation. A series of dsDNAs with different binding affinities was assessed using LILBID laser dissociation curves. The binding affinity results from the LILBID laser dissociation curves strongly correlated with the melting temperatures from UV melting curves and with dissociation constants from isothermal titration calorimetry, standard solution phase methods. LILBID laser dissociation curve data also showed good reproducibility and successfully predicted the melting temperatures and dissociation constants of three DNA sequences. LILBID laser dissociation curves are a promising native mass spectrometry binding affinity method, with reduced time and sample consumption compared to melting curves or titrations.
Reinstatement of Carposina ottawana Kearfott, 1907 (Lepidoptera: Carposinidae) as a valid species
(2020)
Carposina ottawana Kearfott, 1907 (Lepidoptera: Carposinidae), revised status, formerly considered a synonym of C. sasakii Matsumura, 1900, is returned to species status. Morphological features that separate the Asian species C. sasakii and C. niponensis Walsingham, 1900 from the North American C. ottawana are described and illustrated. A heuristic maximum likelihood (ML) analysis based on the mitochondrial gene cyto-chrome oxidase I (DNA barcode) further supports C. ottawana and C. sasakii as distinct taxa.
The intestinal epithelium acts as a selective barrier for the absorption of water, nutrients and orally administered drugs. To evaluate the gastrointestinal permeability of a candidate molecule, scientists and drug developers have a multitude of cell culture models at their disposal. Static transwell cultures constitute the most extensively characterized intestinal in vitro system and can accurately categorize molecules into low, intermediate and high permeability compounds. However, they lack key aspects of intestinal physiology, including the cellular complexity of the intestinal epithelium, flow, mechanical strain, or interactions with intestinal mucus and microbes. To emulate these features, a variety of different culture paradigms, including microfluidic chips, organoids and intestinal slice cultures have been developed. Here, we provide an updated overview of intestinal in vitro cell culture systems and critically review their suitability for drug absorption studies. The available data show that these advanced culture models offer impressive possibilities for emulating intestinal complexity. However, there is a paucity of systematic absorption studies and benchmarking data and it remains unclear whether the increase in model complexity and costs translates into improved drug permeability predictions. In the absence of such data, conventional static transwell cultures remain the current gold-standard paradigm for drug absorption studies.
The Chinese fauna of the pselaphine genus Sathytes Westwood (Batrisitae: Batrisini) currently includes 20 species. In this paper, 15 new species from various provinces of the country are described: S. alpicola sp. nov. (Xizang), S. australis sp. nov. (Guangdong, Guangxi), S. chayuensis sp. nov. (Xizang), S. chengzhifeii sp. nov. (Yunnan), S. huapingensis sp. nov. (Guangxi), S. linzhiensis sp. nov. (Xizang), S. maoershanus sp. nov. (Guangxi), S. nujiangensis sp. nov. (Yunnan), S. panzhaohuii sp. nov. (Xizang), S. shennong sp. nov. (Hubei), S. tianquanus sp. nov. (Sichuan), S. transversus sp. nov. (Xizang), S. valentulus sp. nov. (Guangxi), S. xingdoumontis sp. nov. (Hubei) and S. xizangensis sp. nov. (Xizang). New collection records are provided for S. longitrabis Yin & Li, 2012, S. tangliangi Yin & Li, 2012 and S. yunnanicus Yin & Li, 2012. Maps showing the distribution of the genus in China, and an updated checklist of the world species are provided.
Phenological studies are important to gain insights into the ecology of plant species, particularly those that are threatened and require specific management actions such as regular population monitoring. For many species of terrestrial orchids, limited fundamental knowledge on peak flowering, pollination and seed production restricts effective monitoring outcomes. In this single-season study, phenology data from one population of the vulnerable Diuris praecox were collected, with the aim of informing future management relating to monitoring surveys and to assist in conservation of this species. To this end, six sub-populations (three each in forest habitat and along maintained powerline easements) were visited weekly from the onset of flowering until seed release, with observations made on 134 tagged individuals within 10 x 10 m plots. During the 2019 flowering season, 37% of all plants developed capsules, and 35% released seed. However, success varied between locations, with greater floral displays along powerline easements resulting in stronger pollination rates, while sparse sub-populations in forested locations showed lower pollination. Significantly more flowers per inflorescence (range 1-7) were evident in forest than easement sites, but there was no significant difference in inflorescence height across these habitats. For most sub-populations at least one orchid set seed, even when occurring in low densities (<10 plants). Overall, substantial floral displays did not necessarily result in abundant fruiting, and impacts from desiccation, predation and grazing likely prevented more successful capsule production in any given sub-population. The synchronously flowering shrubs Daviesia ulicifolia and Pultenaea villosa co-occurred across all sub-populations, suggesting that the nectar-less Diuris praecox may mimic these species to attract pollinators. Peak flowering was determined to be approximately 20 days from the onset of flowering, with 83% of all plants in flower at that time. For ongoing monitoring, the timing of surveys to occur approximately three weeks after the first observed flowering, will likely maximize return-for-effort, particularly when survey resources are limited, although it is acknowledged that different seasons and populations may vary from this timeframe.
Large spines are stable and important for memory trace formation. The majority of large spines also contains synaptopodin (SP), an actin-modulating and plasticity-related protein. Since SP stabilizes F-actin, we speculated that the presence of SP within large spines could explain their long lifetime. Indeed, using 2-photon time-lapse imaging of SP-transgenic granule cells in mouse organotypic tissue cultures we found that spines containing SP survived considerably longer than spines of equal size without SP. Of note, SP-positive (SP+) spines that underwent pruning first lost SP before disappearing. Whereas the survival time courses of SP+ spines followed conditional two-stage decay functions, SP-negative (SP-) spines and all spines of SP-deficient animals showed single-phase exponential decays. This was also the case following afferent denervation. These results implicate SP as a major regulator of long-term spine stability: SP clusters stabilize spines, and the presence of SP indicates spines of high stability.
This paper introduces the Kam version of the Multilingual Assessment Instrument for Narratives (LITMUS-MAIN). Kam is a minority language in southern China which belongs to the Kam-Tai language family and is spoken by the Kam ethnic minority people. Adding Kam to MAIN not only enriches the typological diversity of MAIN but also allows researchers to study children’s narrative development in a sociocultural context vastly distinctly different from the frequently examined WEIRD (Western, Educated, Industrialized, Rich, and Democratic) societies. Moreover, many Kam-speaking children are bilingual ethnic minority children who are “left-behind” children living in Mainland China, growing up in a unique socio-communicative environment
Cloeon perkinsi was described from South Africa in 1932 by Barnard. Despite being relatively common in Africa, it was mentioned in the literature quite rarely, and its known distribution to date includes most of sub-Saharan Africa. Material collected recently in Ethiopia, Israel, Saudi Arabia, and Yemen extends its distribution in East Africa, Arabian Peninsula and the Levant. We examined this material, and provide a re-description of adults (females and males) and nymphs of the species. It represents a much-needed urge mainly due to inconsistencies in literature reports regarding colouration, and sometimes incomplete morphological description of all stages. We demonstrate the intraspecific morphological variability that we have witnessed, and provide information regarding the range of habitats colonised by C. perkinsi. Based on geological and climatic history of the studied region, taken together with among countries genetic distances of the mitochondrial barcoding gene COI, we propose colonisation mechanisms for the north-easternmost limit of distribution. The fragmented distribution pattern of the species highlights the conservation importance of isolated aquatic habitats in the region, as well as current knowledge gaps.
Background: Chronic autoimmune demyelinating polyneuropathies (CADP) result in impaired sensorimotor function. However, anecdotal clinical observations suggest the development of cognitive deficits during the course of disease.
Methods: We tested 16 patients with CADP (11 patients with chronic inflammatory demyelinating polyneuropathy, 4 patients with multifocal motor neuropathy and 1 patient with multifocal acquired demyelinating sensory and motor neuropathy) and 40 healthy controls (HC) with a neuropsychological test battery. Blood-brain-barrier dysfunction (BBBd) in patients was assessed retrospectively by analysing the cerebral spinal fluid (CSF) status at the time the diagnosis of CAPD was established.
Results: CADP patients failed on average in 1.7 out of 9 neuropsychological tests (SD ± 1.25, min. 0, max. 5). 50% of the CADP patients failed in at least two neuropsychological tests and 44.3% of the patients failed in at least two different cognitive domains. CADP patients exhibiting BBBd at the time of first diagnosis failed in more neuropsychological tests than patients with intact integrity of the BBB (p < 0.05). When compared directly with the HC group, CADP patients performed worse than HC in tests measuring information processing ability and speed as well as phonemic verbal fluency after adjusting for confounding covariates.
Conclusions: Our results suggest that mild to moderate cognitive deficits might be present in patients with CAPD. One possible tentative explanation, albeit strong evidence is still lacking for this pathophysiological mechanism, refers to the effect of autoimmune antibodies entering the CNS via the dysfunctional blood-brain barrier typically seen in some of the CADP patients.
Three species of the genus Cryptochetum Rondani, 1875 from China are described and figured as new to science: C. euthyiproboscise sp. nov., C. glochidiatusum sp. nov., and C. longilingum sp. nov. An identification key to the known species of Cryptochetum from China is presented. The type specimens of the new species are deposited in the Henan Agricultural University.
Mobile genetic elements (MGEs), especially multidrug-resistance plasmids, are major vehicles for the dissemination of antimicrobial resistance determinants. Herein, we analyse the MGEs in three extensively drug-resistant (XDR) Klebsiella pneumoniae isolates from Germany. Whole genome sequencing (WGS) is performed using Illumina and MinION platforms followed by core-genome multi-locus sequence typing (MLST). The plasmid content is analysed by conjugation, S1-pulsed-field gel electrophoresis (S1-PFGE) and Southern blot experiments. The K. pneumoniae isolates belong to the international high-risk clone ST147 and form a cluster of closely related isolates. They harbour the blaOXA-181 carbapenemase on a ColKP3 plasmid, and 12 antibiotic resistance determinants on an multidrug-resistant (MDR) IncR plasmid with a recombinogenic nature and encoding a large number of insertion elements. The IncR plasmids within the three isolates share a high degree of homology, but present also genetic variations, such as inversion or deletion of genetic regions in close proximity to MGEs. In addition, six plasmids not harbouring any antibiotic resistance determinants are present in each isolate. Our study indicates that genetic variations can be observed within a cluster of closely related isolates, due to the dynamic nature of MGEs. The mobilome of the K. pneumoniae isolates combined with the emergence of the XDR ST147 high-risk clone have the potential to become a major challenge for global healthcare.
Mit spitzer Feder
(2020)
Humor ist, wenn man trotzdem lacht. Im Fall des Klimawandels und angrenzender Themen kann es allerdings durchaus passieren, dass einem dabei der ein oder andere Gluckser schmerzhaft im Halse stecken bleibt. Dem Berliner Zeichner und Karikaturisten Freimut Wössner gelingt es wie kaum einem anderen, die kleinen und großen Unzulänglichkeiten menschlicher Individuen mit der Feder aufzuspießen. Der Themenkreis Klimakrise und Umweltschutz bietet hierfür viel Stoff: Maßlose Konsumgelüste und unreflektierte Bequemlichkeit, dabei aber den Umweltschutz immer wacker auf den Lippen – niemand ist wirklich ganz davor gefeit und bekommt von Wössner einen Spiegel vorgehalten. Vielleicht helfen dem gebürtigen Schwaben dabei seine acht Semester Psychologiestudium, die er in München, Marburg und Saarbrücken absolviert hat. F.W. Bernstein nannte Wössner einst einen »Chronisten unseres postmodernen Biedermeiers«
Als High-End-TV-Drama sprengt die HBO-Serie "Game of Thrones" nicht nur regelmäßig Zuschauerrekorde, sondern ist auch als progressives Serial-Format unter dem Aspekt der seriellen Narration richtungsweisend. Ihre komplexe Handlungsstruktur verdankt die Produktion des US-Pay-TV-Senders der Verortung in einem mittelalterlich anmutenden, von Konflikten dominierten Fantasy-Universum mit mehreren 'Brennpunkten' und einem umfangreichen Charakterinventar. Ebenso wie ihre literarische Vorlage, George R. R. Martins Fantasy-Saga "A Song of Ice and Fire" (seit 1996), präsentiert die Serie den Machtkampf zwischen den verschiedenen Adelsfamilien. Eine Untersuchung der äußerst verschachtelten seriellen Strukturen von "Game of Thrones" vermag die erzählerischen Techniken sowie deren für die Zuschauerbindung essentiellen Funktionsweisen offenzulegen, und bietet so einen Erklärungsansatz für den Publikumserfolg durch die Annahme eines kausalen Zusammenhangs zwischen komplexem Narrationsgefüge, der Art und Weise der Darbietung, und Rezeptionsverhalten. Die vorliegende Analyse von "Game of Thrones" vollzieht sich aus diesem Grunde in zwei Schritten: In einem ersten Teil soll zunächst die Produktion als Ganzes anhand ihrer spezifischen Merkmale serieller Narration charakterisiert werden. Als Fallbeispiel einer strukturbildenden seriellen Sequenz rückt sodann in einem ausführlichen zweiten Teil die herrschaftliche (Selbst-)Legitimation King Joffreys in der Abgrenzung zu weiteren Herrschergestalten in den Blick, der sich durch die Fragwürdigkeit seines Thronanspruchs dazu veranlasst sieht, seine Macht wie kein anderer zu zementieren. Auf welche Art und Weise Joffrey dies mittels typisch höfischer, und zwar ikonographisch-medialer, d. h. visueller Verfahren bewerkstelligt, bildet einen Schwerpunkt des vorliegenden Beitrags.
Ataxia telangiectasia (A-T) is a devastating multi-system disorder characterized by progressive cerebellar ataxia and immunodeficiency. The neurological decline may be caused by multiple factors of which ongoing inflammation and oxidative stress may play a dominant role. The objective of the present investigation was to determine cerebrospinal fluid (CSF) proteins and possible low-grade inflammation and its relation to age and neurological deterioration. In the present study, we investigated 15 patients with A-T from 2 to 16 years. Our investigation included blood and CSF tests, clinical neurological examination, A-T score, and MRI findings. The albumin ratio (AR) was analyzed to determine the blood–brain-barrier function. In addition, inflammatory cytokines (IL-1α, IL-6, IL-8, IL-12 p40, IL-17A, IFN-γ, TNF-α) were measured by the multiplex cytometric bead array. We compared the results with those from an age-matched control group. Three of the A-T patients were analyzed separately (one after resection of a cerebral meningioma, one after radiation and chemotherapy due to leukemia, one after stem cell transplantation). Patient had significantly more moderate and severe side effects due to CSF puncture (vomiting, headache, need for anti-emetic drugs) compared with healthy controls. Total protein, albumin, and the AR increased with age indicating a disturbed blood barrier function in older children. There were no differences for cytokines in serum and CSF with the exception of IL-2, which was significantly higher in controls in serum. The AR is significantly altered in A-T patients, but low-grade inflammation is not detectable in serum and CSF.
Analyse der Genauigkeit des neurochirurgischen Operationsroboters Robotic Surgery Assistant (ROSA)
(2020)
In der vorliegenden Arbeit sollte untersucht werden, ob der Roboter ROSA bei der Durchführung von intrakraniellen Biopsien oder Elektrodenimplantationen eine Alternative zur klassischen, rahmenbasierten Stereotaxie darstellt. Dazu sollte die mechanische und die Anwendungsgenauigkeit des Systems ermittelt werden. Zur Bestimmung der mechanischen Genauigkeit wurde eine experimentelle Phantomstudie durchgeführt. Hier wurden durch den Roboter wiederholt zehn Trajektorien an einem Stereotaxiephantom angefahren. Der Abstand der robotischen Nadel zum Zielpunkt im Phantom wurde anhand von Röntgenbildern bestimmt. Die Wiederholung des Versuchsaufbaus unter Variation der Planungsbildgebung erlaubte den Vergleich verschiedener Schichtdicken sowie zwischen low-dose und normal-dose Verfahren. Die Anwendungsgenauigkeit sollte durch die Analyse operativer Ergebnisse der ROSA erfasst werden. Dazu wurde anhand von postoperativen Bildern die Genauigkeit anhand des Abstands zwischen geplanter und tatsächlicher Lage von Stereoelektroenzephalographie-Elektroden ermittelt. Es wurden verschiedene Referenzierungstechniken, die der Orientierung des Roboters dienen und bei denen eine präoperative Planungsbildgebung (CT oder MRT) mit einem Abbild des OP-Gebietes (durch Oberflächenerkennung oder durch einen Stereotaxierahmen) referenziert wird, verglichen, nämlich CT-Laser; CT-Leksell-Rahmen und MRT-Laser. Die Ergebnisse wurden einer statistischen Analyse unterzogen. Dabei zeigte sich, dass der ROSA-Roboter eine sehr hohe mechanische Genauigkeit im Submillimeterbereich erreicht. Genauigkeitseinbußen bei einer größeren Schichtdicke der zur Planung verwendeten Computertomographie sind messbar, aber gering. Ein signifikanter Einfluss bei der Verwendung eines low-dose-Protokolls konnte nicht festgestellt werden. Dennoch zeigte sich, dass der entscheidende Teil der Ungenauigkeiten in der klinischen Anwendung entsteht und dabei insbesondere durch die Referenzierungstechnik bestimmt wird. Referenzierungen, die auf einer Computertomographie basierten, erwiesen sich als zufriedenstellend genau und als konkurrenzfähig zur konventionellen Methode. Der Unterschied zwischen dem rahmenbasierten und dem auf Oberflächenerkennung basierenden Verfahren war dabei so gering, dass letzteres sich angesichts seiner Vorteile in der Anwendung als besonders günstiges Verfahren hervortut. Im Gegensatz dazu stand das MRT-Laser-Verfahren, welches bei relativ hohen Abweichungen nur eingeschränkt anwendbar scheint und sich damit eher für Anwendungsbereiche mit geringeren Genauigkeitsanforderungen eignet, wie bspw. Biopsien. Weiterhin kann der Verlauf der Trajektorie an den höheren Sicherheitsabstand angepassten werden. Bei der Einordnung der ermittelten Genauigkeiten ist zu beachten, dass es viele weitere, von der Referenzierungs- und Bildgebungsmethode unabhängige Einflussfaktoren gibt. In dieser Arbeit war der Einfluss der erfassten externen Paramter zwar limitiert, bei anderen Autoren zeigte sich jedoch ein signifikanter Effekt. Dennoch deckt sich die Gesamtgenauigkeit mit den Ergebnissen anderer Arbeiten.
In Zusammenschau der Ergebnisse weist die vom ROSA-Assistenzsystem assistierte Stereotaxie eine verbesserte Prozessqualität auf, unter anderem durch die erhebliche Zeitersparnis, ggf. der Wegfall des Transports des narkotisierten Patienten, die Adaptionsmöglichkeiten der Prozessteilschritte an den Patienten, sowie eine hohe Nutzerfreundlichkeit. Entscheidend ist jedoch, dass es sich um ein sehr sicheres Verfahren handelt: Durch die hohe Genauigkeit wird das Operationsrisiko minimiert, gleichzeitig erlauben Laser-gestützte Registrierungsverfahren eine Reduktion der Strahlenexposition. Zur Konsolidierung der in dieser Arbeit gewonnenen Erkenntnisse sind weitere klinische Daten notwendig.
Der hier edierte und übersetzte Text ist Teil einer Sammelrezension ("Poésie"), in der Teodor de Wyzewa 1887 im Februar-Heft der "Revue indépendante" neue Lyrikbände bespricht.
Sie sind ihm Anlass eines grundsätzlichen Nachdenkens über Symbolismus, insofern dieser als eine neue Schreibweise der Lyrik im Gespräch ist und, so Wyzewa, es der Klärung des Symbolbegriffs bedarf, auf den der 1887 bereits geläufige Name der neuen Bewegung verweist.
The β-carboline alkaloid harmine is a potent DYRK1A inhibitor, but suffers from undesired potent inhibition of MAO-A, which strongly limits its application. We synthesized more than 60 analogues of harmine, either by direct modification of the alkaloid or by de novo synthesis of β-carboline and related scaffolds aimed at learning about structure-activity relationships for inhibition of both DYRK1A and MAO-A, with the ultimate goal of separating desired DYRK1A inhibition from undesired MAO-A inhibition. Based on evidence from published crystal structures of harmine bound to each of these enzymes, we performed systematic structure modifications of harmine yielding DYRK1A-selective inhibitors characterized by small polar substituents at N-9 (which preserve DYRK1A inhibition and eliminate MAO-A inhibition) and beneficial residues at C-1 (methyl or chlorine). The top compound AnnH75 remains a potent DYRK1A inhibitor, and it is devoid of MAO-A inhibition. Its binding mode to DYRK1A was elucidated by crystal structure analysis, and docking experiments provided additional insights for this attractive series of DYRK1A and MAO-A inhibitors.
Human lymph nodes play a central part of immune defense against infection agents and tumor cells. Lymphoid follicles are compartments of the lymph node which are spherical, mainly filled with B cells. B cells are cellular components of the adaptive immune systems. In the course of a specific immune response, lymphoid follicles pass different morphological differentiation stages. The morphology and the spatial distribution of lymphoid follicles can be sometimes associated to a particular causative agent and development stage of a disease. We report our new approach for the automatic detection of follicular regions in histological whole slide images of tissue sections immuno-stained with actin. The method is divided in two phases: (1) shock filter-based detection of transition points and (2) segmentation of follicular regions. Follicular regions in 10 whole slide images were manually annotated by visual inspection, and sample surveys were conducted by an expert pathologist. The results of our method were validated by comparing with the manual annotation. On average, we could achieve a Zijbendos similarity index of 0.71, with a standard deviation of 0.07.