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Aim: Participation of medical students in the conceptual development of targeted and attractive teaching content for rural areas.
Method: A questionnaire was developed to gather information on students' views of their current medical studies, career interests, and what requirements should be met by an optional rural health program in general practice. By means of an online survey in summer 2015, all medical students from the fourth preclinical semester onwards (n=2,150) at Goethe University Frankfurt were surveyed on one occasion. Statistical analysis was mainly descriptive. Personal attitudes towards a career as a family practitioner were examined for statistical significance. Further information was gathered on whether a measurable correlation exists between personal background and desired work location.
Results: Of the 2,150 students that were contacted, 617 participated in the survey (response rate=28.7%). The results covered a wide range of ideas and recommendations and were representative both of medical students with a positive attitude toward general practice, as well as those that were rather critical of teaching in general practice. The students expected the planned health program to be of strong practical relevance and to acquaint them with the administrative and economic aspects of running a practice.
Conclusions: By including the target group in the development process, it was possible to tailor the health program to meet the needs of future participants more precisely. Student participation can also be expected to result in greater acceptance of the program. The results on teaching content may also provide other medical faculties with orientation when developing comparable programs.
The blue light-dependent interaction between the proteins iLID and Nano allows recruiting and patterning proteins on GUV membranes, which thereby capture key features of patterns observed in nature. This photoswitchable protein interaction provides non-invasive, reversible and dynamic control over protein patterns of different sizes with high specificity and spatiotemporal resolution.
We present an abundance-based checklist of Pennsylvania planthoppers (Hemiptera: Auchenorrhyncha: Fulgoroidea) compiled from available literature and 13,718 specimens. A substantial portion of the latter were bycatch from Lindgren funnel and panel traps intended to intercept wood-boring beetle species, and a directed survey for the spotted lanternfly (Lycorma delicatula (White)). The known planthopper fauna of Pennsylvania consists of 10 families, 54 genera and 139 species including 34 new state species records (and 12 new genera). In an attempt to assess the level of completeness of this survey, we compiled an abundance-based checklist of planthopper species found in states adjacent to Pennsylvania and found similar numbers of planthopper species for each state (viz. Delaware 138 species, Maryland 147, New Jersey 145, New York 162 and Ohio 126), but the cumulative species list is comprised of 240 planthopper species, suggesting that the inventory for Pennsylvania and all adjacent states may be substantially incomplete.
Rhagoletis cerasi (Linnaeus) (Diptera: Tephritidae) is reported from Mississauga, Ontario, Canada, and Niagara County, New York, United States for the first time, new records. Specimens from Ontario were collected in 2016, and New York in 2017. This fly is subject to regulatory control and poses a risk to cherry and honeysuckle in North America.
The new edition of the 2016 World Health Organization (WHO) classification system for tumors of the hematopoietic and lymphoid tissues was published in September 2017. Under the category of myeloproliferative neoplasms (MPNs), the revised document includes seven subcategories: chronic myeloid leukemia, chronic neutrophilic leukemia, polycythemia vera (PV), primary myelofibrosis (PMF), essential thrombocythemia (ET), chronic eosinophilic leukemia-not otherwise specified and MPN, unclassifiable (MPN-U); of note, mastocytosis is no longer classified under the MPN category. In the current review, we focus on the diagnostic criteria for JAK2/CALR/MPL mutation-related MPNs: PV, ET, and PMF. In this regard, the 2016 changes were aimed at facilitating the distinction between masked PV and JAK2-mutated ET and between prefibrotic/early and overtly fibrotic PMF. In the current communication, we (i) provide practically useful resource tables and graphs on the new diagnostic criteria including outcome, (ii) elaborate on the rationale for the 2016 changes, (iii) discuss the complementary role of mutation screening, (iv) address ongoing controversies and propose solutions, (v) attend to the challenges of applying WHO criteria in routine clinical practice, and (vi) outline future directions from the perspectives of the clinical pathologist.
Auswirkung der Chemisorption von Organothiolaten auf den elektrischen Widerstand dünner Goldfilme
(2018)
Hochgeordnete Monolagen von Organothiolaten auf Goldoberflächen bilden sich bei Kontakt einer Goldoberfläche mit einer Lösung eines Thiols oder Thioacetats spontan aus. Die Adsorption auf dünnen Metallfilmen mit Schichtdicken im Bereich von 25 - 100 nm führt zu einer Änderung des elektrischen Widerstandes des Films, die an Goldfilmen mit Schichtdicken von 25 - 40 nm über eine einfache Zweipunktmessung verfolgt wurde. Die Proportionalität der Widerstandsänderung mit der Menge an adsorbiertem Material konnte für die in dieser Arbeit verwendeten Dünnschichtsensoren bestätigt werden. Zu diesem Zweck wurden gleichzeitig Widerstands- und Oberflächenplasmonenresonanzmessungen an 40 nm starken Goldfilmen durchgeführt. In diesen Experimenten zeigt sich die Widerstandsmessung zur Beobachtung der Adsorptionskinetik als die überlegene Technologie.
Die durch Mikrokontaktdrucken und Freiätzen der gedruckten Strukturen hergestellten Sensoren zeigen eine individuelle Signalintensität. Die Normierung auf die maximale, durch Belegung mit Hexadecanthiol (HDT) oder Dodecanthiol erreichte, Signalstärke ermöglichte den Vergleich der maximalen Signalstärke von Thiolatmonolagen, die durch Belegung mit n-Alkanthiolen (CH_3(CH_2)_(n-1)-SH mit n = 12, 16, 19, 22 und 33, Cn), 11-Mercaptoundecyl-hexaethylenglycol (HSC11EG6OH), Adamantan-1-thiol (AdaSH), Triptycenthiol (TrpSH), Anthracen-2-thiol (Ant-0SH), Anthracen-2-alkanthiolen (Ant-(CH_2)_n-SH mit n = 1 - 5 und 10, Ant-nSH), p-Terphenyl-4-thiol (TP0SH), p-Terphenyl-4-alkanthiolen (TP-(CH_2)_n-SH mit n = 1 - 4, TPnSH) und p-Terphenyl-4-ethanthioacetat (TP2SAc) erzeugt wurden. Die Größe der Widerstandsänderung zeigt eine deutliche Abhängigkeit vom organischen Rest des Oberflächenadsorbats. Für die Verstärkung des Signals wurde die folgende Reihenfolge gefunden: Trp > Ada > Ant-0 > Ant-1 > TP0 > TP1 > Ant-2 > TP2 > Cn (n = 12 - 33) = C11EG6OH = Ant-n (n = 3 - 11) = TPn (n = 3, 4). Bei bekannter Verstärkung des Signals durch ein Adsorbat kann unabhängig von der Oberflächenrauigkeit die Oberflächenbedeckung durch Chemisorbate in einer Güte bestimmt werden, die der durch STM- und TEM-Messungen erreichten vergleichbar ist. Die Methode wurde angewendet, um Schichten von TP2SH und TP2SAc, die bei 20 und 60 °C aus ethanolischer Lösung abgeschieden wurden, zu vergleichen. Die Unterschiede in der Oberflächendichte, die durch eine Erhöhung der Abscheidungstemperatur zu beobachten sind, können durch eine Beschleunigung der Reaktion nach Arrhenius erklärt werden. Auch die Temperaturabhängigkeit der Abscheidungsgeschwindigkeit von HDT aus ethanolischer Lösung an Goldoberflächen, die in einem Bereich von -10 °C bis +30 °C betrachtet wurde, ist mit dem Arrhenius'schen Ansatz konform. Die Aktivierungsenergie der Adsorption von HDT auf Gold wurde auf E_a = 23 +-6 kJ/mol bestimmt.
Die Konzentrationsabhängigkeit der Abscheidung aus ethanolischer Lösung an Goldoberflächen wurde für HDT, AdaSH, TP2SH und TP2SAc untersucht. Um eine Präadsorption der Thiole vor dem eigentlichen Start der Messung zu verhindern, wurde eine Apparatur mit einem Diaphragma aus Aluminium entwickelt, das beim Start der Messung mit dem Sensor durchstoßen wird. Mit Ausnahme von TP2SH zeigen alle Adsorptive ein Adsorptions-Desorptions-Gleichgewicht. Die Adsorptionsisothermen bei 20 °C lassen sich am besten durch die Freundlich-Isotherme beschreiben. Während die Reaktionsordnung im Adsorbat für die Adsorption der Thiole nahe an 1 liegt, hat sie für die Adsorption von TP2SAc einen Wert von ca. 1/4. Damit ergibt sich für die Geschwindigkeitskonstante der Adsorption k_a(HDT) = (2,3 +-0,2) 10^4 L/(mol s), k_a(AdaSH) = (6,1 +-0,2) 10^4 L/(mol s), k_a(TP2SH) = (7,3 +-0,4) 10^3 L/(mol s) und k_a(TP2SAc) = (8 +-3) 10^-2 L^(1/4)/(mol^(1/4) s). Die Adsorptionskurven der Thiole weisen bei Konzentrationen unterhalb von 5 10^-5 mol/L einen linearen Bereich auf, der einer zwischenzeitlichen Diffusionskontrolle zugeordnet wird.
An die aufgenommenen Adsorptionskurven der Thiole wurden literaturbekannte Modelle numerisch angepasst und teilweise weiterentwickelt. Die Anpassung konnte durch die Einführung einer vor der Oberfläche gelagerten Diffusionsgrenzschicht, in welcher der zeitabhängige Verlauf der Analytkonzentration in einem System von 10 Schichten berechnet wurde, deutlich verbessert werden. Von allen getesteten Modellen zeigt nur die Adsorption mit Ausschlussmuster keine Konzentrationsabhängigkeit der Geschwindigkeitskonstante der Desorption. Dieses Modell bezieht den Verlust von Adsorptionsplätzen mit ein, die einem besetzten Adsorptionsplatz benachbart sind und durch das adsorbierte Teilchen verdeckt werden. Der daraus resultierende Zusammenhang zwischen der Konzentration freier Adsorptionsplätze und dem Bedeckungsgrad der Oberfläche Theta_F(Theta) ist abhängig vom Verhältnis der Stoßfrequenz zwischen den Teilchen und der Oberfläche zur Platzwechselfrequenz der Teilchen auf der Oberfläche. Zur Bestimmung von Theta_F(Theta) für die numerische Anpassung der Adsorptionskurven von HDT und TP2SH wurde die Oberflächenbesetzung in einem Monte-Carlo-Verfahren für eine Konzentrationsreihe in Zehnerpotenzschritten simuliert.
We examine how a firms' investment behavior affects the investment of a neighboring firm. Economic theory yields ambiguous predictions regarding the direction of firm peer effects and consistent with earlier work, we find that firms display similar investment behavior within an area using OLS analysis. Exploiting time-variation in the rise of U.S. states' corporate income taxes and utilizing heterogeneity in firms' exposure to increases in corporate income tax rates, we identify the causal impact of local firms' investments. Using this as an instrumental variable in a 2SLS estimation, we find that an increases in local firms' investment reduces the investment of a local peer firm. This effect is more pronounced if local competition among firms is stronger and supports theories that firm investments are strategic substitutes due to competition.
Delayed-onset muscle soreness (DOMS) is a common symptom in people participating in exercise, sport, or recreational physical activities. Several remedies have been proposed to prevent and alleviate DOMS. In 2008 and 2015, two studies have been conducted to investigate the effects of acupuncture on symptoms and muscle function in eccentric exercise-induced DOMS of the biceps brachii muscle. In 2008 a prospective, randomized, controlled, observer and subject-blinded trial was undertaken with 22 healthy subjects (22–30 years; 12 females) being randomly assigned to three treatment groups: real acupuncture (deep needling at classic acupuncture points and tender points; n = 7), sham-acupuncture (superficial needling at non-acupuncture points; n = 8), and control (n = 7). In 2015, a five-arm randomized controlled study was conducted with 60 subjects (22 females, 23.6 ± 2.8 years). Participants were randomly allocated to needle, laser, sham needle, sham laser acupuncture, and no intervention.
In both cases treatment was applied immediately, 24 and 48 hours after DOMS induction.
The outcome measures included pain perception (visual analogue scale; VAS), mechanical pain threshold (MPT), maximum isometric voluntary force (MIVF) and pressure pain threshold (PPT).
Results: In 2008, following nonparametric testing, there were no significant differences between groups in outcome measures at baseline. After 72 hours, pain perception (VAS) was significantly lower in the acupuncture group compared to the sham acupuncture and control subjects. However, the mean MPT and MIVF scores were not significantly different between groups. This lead to the conclusion, that acupuncture seemed to have no effects on MPT and muscle function, but reduced perceived pain arising from exercise-induced DOMS.
The more recent results from 2015 indicated that neither verum nor sham interventions significantly improved outcomes within 72 hours when compared with the no treatment control (P > 0.05).
Cell–matrix adhesion and cell migration are physiologically important processes that also play a major role in cancer spreading. In cultured cells, matrix adhesion depends on integrin-containing contacts such as focal adhesions. Flotillin-1 and flotillin-2 are frequently overexpressed in cancers and are associated with poor survival. Our previous studies have revealed a role for flotillin-2 in cell–matrix adhesion and in the regulation of the actin cytoskeleton. We here show that flotillins are important for cell migration in a wound healing assay and influence the morphology and dynamics of focal adhesions. Furthermore, anchorage-independent growth in soft agar is enhanced by flotillins. In the absence of flotillins, especially flotillin-2, phosphorylation of focal adhesion kinase and extracellularly regulated kinase is diminished. Flotillins interact with α-actinin, a major regulator of focal adhesion dynamics. These findings are important for understanding the molecular mechanisms of how flotillin overexpression in cancers may affect cell migration and, especially, enhance metastasis formation.
Background: Definite diagnosis and therapeutic management of cholangiocarcinoma (CCA) remains a challenge. The aim of the current study was to investigate feasibility and potential impact on clinical management of targeted sequencing of intraductal biopsies.
Methods: Intraductal biopsies with suspicious findings from 16 patients with CCA in later clinical course were analyzed with targeted sequencing including tumor and control benign tissue (n = 55 samples). A CCA-specific sequencing panel containing 41 genes was designed and a dual strand targeted enrichment was applied.
Results: Sequencing was successfully performed for all samples. In total, 79 mutations were identified and a mean of 1.7 mutations per tumor sample (range 0–4) as well as 2.3 per biopsy (0–6) were detected and potentially therapeutically relevant genes were identified in 6/16 cases. In 14/18 (78%) biopsies with dysplasia or inconclusive findings at least one mutation was detected. The majority of mutations were found in both surgical specimen and biopsy (68%), while 28% were only present in biopsies in contrast to 4% being only present in the surgical tumor specimen.
Conclusion: Targeted sequencing from intraductal biopsies is feasible and potentially improves the diagnostic yield. A profound genetic heterogeneity in biliary dysplasia needs to be considered in clinical management and warrants further investigation.
Translational impact: The current study is the first to demonstrate the feasibility of sequencing of intraductal biopsies which holds the potential to impact diagnostic and therapeutical management of patients with biliary dysplasia and neoplasia.
Background: There currently are no internationally recognised treatment guidelines for patients with advanced gastric cancer/gastro-oesophageal junction cancer (GC/GEJC) in whom two prior lines of therapy have failed. The randomised, phase III JAVELIN Gastric 300 trial compared avelumab versus physician’s choice of chemotherapy as third-line therapy in patients with advanced GC/GEJC.
Patients and methods: Patients with unresectable, recurrent, locally advanced, or metastatic GC/GEJC were recruited at 147 sites globally. All patients were randomised to receive either avelumab 10 mg/kg by intravenous infusion every 2 weeks or physician’s choice of chemotherapy (paclitaxel 80 mg/m2 on days 1, 8, and 15 or irinotecan 150 mg/m2 on days 1 and 15, each of a 4-week treatment cycle); patients ineligible for chemotherapy received best supportive care. The primary end point was overall survival (OS). Secondary end points included progression-free survival (PFS), objective response rate (ORR), and safety.
Results: A total of 371 patients were randomised. The trial did not meet its primary end point of improving OS {median, 4.6 versus 5.0 months; hazard ratio (HR)=1.1 [95% confidence interval (CI) 0.9–1.4]; P= 0.81} or the secondary end points of PFS [median, 1.4 versus 2.7 months; HR=1.73 (95% CI 1.4–2.2); P> 0.99] or ORR (2.2% versus 4.3%) in the avelumab versus chemotherapy arms, respectively. Treatment-related adverse events (TRAEs) of any grade occurred in 90 patients (48.9%) and 131 patients (74.0%) in the avelumab and chemotherapy arms, respectively. Grade ≥3 TRAEs occurred in 17 patients (9.2%) in the avelumab arm and in 56 patients (31.6%) in the chemotherapy arm.
Conclusions: Treatment of patients with GC/GEJC with single-agent avelumab in the third-line setting did not result in an improvement in OS or PFS compared with chemotherapy. Avelumab showed a more manageable safety profile than chemotherapy.
Trial registration: ClinicalTrials.gov: NCT02625623.
The Luck Charm
(2018)
Tomasi Manda, an intelligent boy whose rational mind rejects belief in witchcraft, does something that causes his mother and elder brother to fear that he might be bewitched. They decide to put 'protective medicine' into his blood. But their problem is how to get Tomasi to accept the medicine, having once before failed to convince him to have such protection. However, when Tomasi passes his primary school examinations and is selected for a boarding secondary school away from home, the two approach him with the medicine disguised as a charm, something that would bring him good luck from the strangers among whom he will now be living. Tomasi initially rejects the o?er, but when, to his surprise, he sees that this causes his mother great pain, he lets her insert into his blood 'the totally useless powder.' Then certain things begin to happen to Tomasi which, unable to explain them otherwise, he can't help thinking are being caused by the potion his mother has put in his blood. Eventually he becomes convinced that he now has a potent luck charm in his body, and reaches the frightening conclusion that from now on his life will be run by this charm. What is he to do?
Sekani's Solution
(2018)
Andreya Soko manages to win the love of his college mate, Sekani Zuza, the most beautiful, most sought-after girl in college. After ?nishing college, Andreya works hard to save for Sekani's bride price from his meager salary as a primary school teacher. From the same slim salary he also struggles to ?nance the education of his younger brothers. When his parents get killed in an accident and the problems providing the bride price are further increased, Sekani steps in with an unusual solution...
The missionary work of the Seventh-day Adventist Church started in Southern Malawi in 1902, and histories of churches are usually told from that starting point. This book uses a different approach, it tells the story of Lunjika Mission (earlier called Mombera Mission) which begins in 1932, showing how the SDA Church met a new culture, that of the strongly patrilineal Ngoni and their neighbours to the North, and how it dealt with other churches that had started missionary work in that broad area up to two generations before.
Aim: To evaluate the ability of PillCamColon2 to visualize colonic segments missed by incomplete optical colonoscopy (OC) and to assess the diagnostic yield.
Methods: This prospective multicentre study included 81 patients from nine centres who underwent second-generation colon capsule endoscopy (CCE) following incomplete OC performed by an experienced gastroenterologist (> 1000 colonoscopies). Patients with stenosis were excluded. According to patient preferences, CCE was performed the following day (protocol A) after staying on clear liquids and 0.75 L Moviprep in the morning or within 30 d after new split-dose Moviprep (protocol B). Boosts consisted of 0.75 L and 0.25 L Moviprep, and phospho-soda was given as a rescue if the capsule was not excreted after seven hours.
Results: Seventy-four patients were analysed (51% of them in group A; 49% in group B). Bowel cleansing was adequate in 67% of cases, and CCE could visualize colonic segments missed by incomplete colonoscopy in 90% of patients under protocol A and 97% of patients under protocol B (P = 0.35, n.s.). Significant polyps including adenocarcinoma were detected in 24% of cases. Detection rates for all polyps and significant polyps per patient were similar in both protocols. Polyps were found predominantly in the right colon (86%) in segments that were not reached by OC. Extracolonic findings - such as reflux esophagitis, suspected Barrett esophagus, upper GI-bleeding, gastric polyps, gastric erosions and angiectasia - were detected in eight patients. PillCamColon2 capsule was retained in the ileum of one patient (1.4%) without symptoms and removed during an uneventful resection for unknown Crohn’s disease that was diagnosed as the cause of anemia, which was the indication for colonoscopy. CCE was well tolerated. One patient suffered from self-limiting vomiting after consuming the phospho-soda.
Conclusion: Second-generation CCE using a low-volume preparation is useful after incomplete OC, and it allows for the detection of additional relevant findings, but cleansing efficiency could be improved.
Background. The purpose of this systematic review was to accurately assess the procedural success of ridge preservation technique through the application of strict inclusion and exclusion criteria.
Data Sources. A methodical search of PubMed of the US National Library of Medicine and the Cochrane Central Register of Controlled Trials was conducted for applicable articles. Only randomized controlled trials comparing ridge preservation treatment with a nongrafting control, ten-subject minimum sample size, and three or more months of follow-up were included in our study.
Types of Studies Reviewed. In a screening between January 1980 and September 2017, articles meeting predetermined criteria were further examined in a qualitative data analysis. A thorough search of the databases provided 1876 articles. Of these records, 174 were assessed for eligibility through the systematic employment of inclusion and exclusion criteria.
Results. Two records were appropriate for further data analysis. One study used a mixture of a deproteinized cancellous bovine bone and porcine collagen fibers in a block form (DBB/CF), while the other study used leukocyte-platelet-rich fibrin (L-PRF). The use of DBB/CF reduced the magnitude of vertical bone resorption, yet the study showed high risk of bias. The use of L-PRF reduced the magnitude of both the horizontal and vertical crestal bone resorption; however, the low sample size created wide standard deviations between the test and control groups. Inherent weaknesses were present in both studies. Through methodical analysis of both records, the dissimilarities prevented the conduction of a meta-analysis.
Implications of Key Findings. Within the limitations of this systematic review, L-PRF reduced the magnitude of vertical and horizontal bone resorption, which places L-PRF as a potential material of choice for ridge preservation procedures. Conclusions. Within the limitations and weaknesses of both studies, the use of DBB/CF prevented the vertical crestal bone resorption while the L-PRF prevented both the horizontal and vertical crestal bone resorption. More randomized controlled clinical trials are needed to eliminate all the confounding factors, which bias the outcome of ridge preservation techniques.
Der im Alltag wie auch in medialen Darstellungen immer wieder anzutreffende Befund, dass Arbeit "irgendwie" mit der ganzen Gesellschaft zu tun habe, das heißt auch mit unserem gesamten privaten Leben, lässt sich aus einer doppelten Blickrichtung heraus sehr viel genauer beantworten als es bisher vielfach der Fall war: nämlich erstens vom Spektrum der für den komplexen Bereich der Arbeit relevanten Diskurse aus und zweitens von der medial und sprachlich erfolgenden Zusammenführung dieser Diskurse und des dabei vermittelten Wissens.
The leptonic decay of the charged pion in the presence of background magnetic fields is investigated using quenched Wilson fermions. It is demonstrated that the magnetic field opens up a new channel for this decay. The magnetic field-dependence of the decay constants for both the ordinary and the new channel is determined. Using these inputs from QCD, we calculate the total decay rate perturbatively.
Purpose: Stereotactic radiosurgery (SRS) is an established primary treatment for newly diagnosed brain metastases with high local control rates. However, data about local re-irradiation in case of local failure after SRS (re-SRS) are rare. We evaluated the feasibility, efficacy and patient selection characteristics in treating locally recurrent metastases with a second course of SRS.
Methods: We retrospectively evaluated patients with brain metastases treated with re-SRS for local tumor progression between 2011 and 2017. Patient and treatment characteristics as well as rates of tumor control, survival and toxicity were analyzed.
Results: Overall, 32 locally recurrent brain metastases in 31 patients were irradiated with re-SRS. Median age at re-SRS was 64.9 years. The primary histology was breast cancer and non-small-cellular lung cancer (NSCLC) in respectively 10 cases (31.3%), in 5 cases malignant melanoma (15.6%). In the first SRS-course 19 metastases (59.4%) and in the re-SRS-course 29 metastases (90.6%) were treated with CyberKnife® and the others with Gamma Knife. Median planning target volume (PTV) for re-SRS was 2.5 cm3 (range, 0.1–37.5 cm3) and median dose prescribed to the PTV was 19 Gy (range, 12–28 Gy) in 1–5 fractions to the median 69% isodose (range, 53–80%). The 1-year overall survival rate was 61.7% and the 1-year local control rate was 79.5%. The overall rate of radiological radio-necrosis was 16.1% and four patients (12.9%) experienced grade ≥ 3 toxicities.
Conclusions: A second course of SRS for locally recurrent brain metastases after prior local SRS appears to be feasible with acceptable toxicity and can be considered as salvage treatment option for selected patients with high performance status. Furthermore, this is the first study utilizing robotic radiosurgery for this indication, as an additional option for frameless fractionated treatment.
Gender in Fulani proverbs
(2018)
Presented paper deals with Fulani people of West Africa and with the influence of their way of life on their language. One part of the Fulani people lives nomadic pastoral live, meanwhile another part is sedentary, living in the towns. The authors of the paper pay their attention to the the gender of Fulani proverbs which reflects the way of life of Fulani people.
Myomas, also known as fibroids, are a specific characteristic of the human species. No other primates develop fibroids. At a cellular level, myomas are benign hyperplastic lesions of uterine smooth muscle cells. There are interesting theoretical concepts that link the development of myomas in humans with the highly specific process of childbirth from an upright position and the resulting need for greatly increased “expulsive” forces during labor. Myomas might be the price our species pays for our bipedal and highly intelligent existence. Myomas affect, with some variability, all ethnic groups and approximately 50% of all women during their lifetime. While some remain asymptomatic, myomas can cause significant and sometimes life-threatening uterine bleeding, pain, infertility, and, in extreme cases, ureteral obstruction and death. Traditionally, over 50% of all hysterectomies were performed for fibroids, leading to a significant healthcare burden. In this article, we review the developments of the past 20 years with regard to multiple new treatment strategies that have evolved during this time.
Ataxia telangiectasia (A-T) is a primary immunodeficiency with mutations in the gene encoding the A-T mutated (ATM) protein that interacts with immune, hematopoietic, and endocrine targets resulting in broad multi-systemic clinical manifestations with a devastating outcome. Apart from a progressive neurodegenerative disorder, A-T leads to significantly increased susceptibility to malignancies. It is a matter of discussion whether pre-emptive allogeneic hematopoietic stem cell transplantation (alloHSCT) using a reduced intensity conditioning regimen would be an option to restore immune-competence and prevent malignancy, as shown in animal models, because conventional treatment protocols of malignant diseases using radio- and/or chemotherapy have a high rate of therapy-related morbidity and mortality in these patients. We present the course of the disease, including immune reconstitution and neurological outcome following pre-emptive alloHSCT in a 4-year-old boy with A-T on a 6 year follow-up. Our manuscript provides a proof-of-concept of alloHSCT as an individual pre-emptive treatment strategy from which some A-T patients might benefit.
An ein philosophisches Fachpublikum richtete sich Blumenberg zuerst mit "Die sprachliche Wirklichkeit der Philosophie", geschrieben 1946 und veröffentlicht im Jahr darauf in der Hamburger Akademischen Rundschau. [...] Der Essay von nur vier Seiten zeugt von Blumenbergs Hadern mit allen Versuchen, die Philosophie von Grund auf neu zu errichten. Erstaunlich daran ist nun, dass Blumenberg dabei nicht als Vertreter der Phänomenologie und Anthropologie auftritt, als der er heute vor allem gelesen wird. Stattdessen erscheint er in diesem Anfangstext als Sprachtheoretiker.
Brachiopod shells are the most widely used geological archive for the reconstruction of the temperature and the oxygen isotope composition of Phanerozoic seawater. However, it is not conclusive whether brachiopods precipitate their shells in thermodynamic equilibrium. In this study, we investigated the potential impact of kinetic controls on the isotope composition of modern brachiopods by measuring the oxygen and clumped isotope compositions of their shells. Our results show that clumped and oxygen isotope compositions depart from thermodynamic equilibrium due to growth rate-induced kinetic effects. These departures are in line with incomplete hydration and hydroxylation of dissolved CO2. These findings imply that the determination of taxon-specific growth rates alongside clumped and bulk oxygen isotope analyses is essential to ensure accurate estimates of past ocean temperatures and seawater oxygen isotope compositions from brachiopods.
Mires or peat swamps have a restricted distribution in Australia and are limited to areas where hydrological inputs exceed evapotranspiration. In NSW, mires are restricted to the coast, adjacent ranges or tablelands, and along the Great Dividing Range; most are listed as threatened ecological communities under State or Commonwealth legislation. Due primarily to the relatively high rainfall and suitable geology, the Blue Mountains region includes a number of such threatened mire ecological communities. Most of these mire types are largely included within the Greater Blue Mountains World Heritage Area, although there are notable exceptions, such as the endangered Newnes Plateau Shrub Swamps.
This paper reports on a little-known group of diverse, relatively isolated and largely unprotected mires, in a relatively low rainfall area in the upper Cudgegong River catchment, east of Rylstone in the NSW Central Tablelands, and of their floristic, hydrogeomorphic and typological relationship with other mires of the Blue Mountains. They can be broadly divided into montane bogs, montane fens and hanging swamps. Particular attention is focussed on the largest and most diverse one, Rollen Creek swamp, which contains all three types. It is hoped that highlighting this hitherto unrecognised group of high conservation-value mires will contribute to their improved conservation and encourage further research into mires of eastern NSW.
In der zweiten Hälfte des 19. und am Anfang des 20. Jahrhunderts entwickelten sich in ganz Europa die sogenannten Völkerschauen, in denen populäre Unterhaltungsformen, Inszenierungspraktiken und wissenschaftliche Ansätze eng ineinandergriffen. In Deutschland spielte dabei der Hamburger Tierhändler Carl Hagenbeck eine wesentliche Rolle: Als sein Tierhandel am Anfang der 1870er Jahre in Schwierigkeiten geriet, begann er, Zurschaustellungen fremder, als "exotisch" betrachteter Menschen zu veranstalten, was ihm großen Erfolg einbrachte. Wie bereits mehrfach in der Forschung hervorgehoben, gingen die so entstandenen Völkerschauen mit bestimmten Inszenierungstechniken einher: Es ging darum, das "Exotische" – das heißt hier vor allem die am Ende des 19. Jahrhunderts ein breites Publikum faszinierende körperliche Fremdheit – anschaulich zu machen und sie zugleich in vertraute Darstellungs- und Wahrnehmungskonventionen einzubetten, um den Zuschauern das Fremde zu vermitteln. Hagenbecks Schaustellungen zeichneten sich insbesondere durch ihre genau durchdachten, auf dramatischen Strukturen und auf melodramatischen Motiven beruhenden Attraktionen aus – wie Überfall und Frauenentführung –, die es ermöglichen, Verbindungslinien zwischen Völkerschauen und Theaterkunst zu ziehen. Es lässt sich zeigen, dass die Art und Weise, wie diese "exotischen" Menschen inszeniert wurden, vom wissenschaftlichen Blick der Anthropologen sowie von der Kooperation zwischen Anthropologen und Schaustellern beeinflusst wurde. Es soll gefragt werden, inwiefern Spuren der Völkerschauen im europäischen Theater der Jahrhundertwende um 1900 aufzufinden sind: Inwieweit übten anthropologisierte Inszenierungen fremder Völker einen Einfluss auf den Retheatralisierungsprozess des Theaters aus? Inwiefern entstand das moderne Theaterverständnis aus einer Anthropologisierung des Theaters?
Challenges of FAIR phase 0
(2018)
After two-year's shutdown, the GSI accelerators plus the latest addition of storage ring CRYRING, will be back into operation in 2018 as the FAIR phase 0 with the goal to fulfill the needs of scientific community and the FAIR accelerators and detector development. Even though GSI has been well known for its operation of a variety of ion beams ranging from proton up to uranium for multi research areas such as nuclear physics, astrophysics, biophysics, material science, the upcoming beam time faces a number of challenges in re-commissioning its existing circular accelerators with brand new control system and upgrade of beam instrumentations, as well as in rising failures of dated components and systems. The cycling synchrotron SIS18 has been undergoing a set of upgrade measures for fulfilling future FAIR operation, among which many measures will also be commissioned during the upcoming beam time. This paper presents the highlights of the challenges such as re-establishing the high intensity heavy ion operation as well as parallel operation mode for serving multi users. The status of preparation including commissioning results will also be reported.
Bebilderte Multiple-Choice- (MC) Fragen sind ein integraler Bestandteil von schriftlichen Prüfungen in der Anatomie. In bebilderten MC-Fragen bezieht sich die schriftliche Frage auf verschiedene Typen von Abbildungen wie Röntgenaufnahmen, Mikrofotografien von histologischen Schnitten oder Zeichnungen von anatomischen Strukturen. Da das Hereinnehmen von Abbildungen in MC-Fragen das Abschneiden der Items beeinflussen kann, verglichen wir die Charakteristika von anatomischen Items getestet mit bebilderten und nicht bebilderten MC-Fragen in sieben Anatomieklausuren und in zwei schriftlichen Teilen des Ersten Abschnitts der Ärztlichen Prüfung (M1).
In dieser Studie verglichen wir 25 bebilderte und 163 nicht bebilderte MC-Fragen aus Anatomieklausuren und 27 bebilderte und 130 nicht bebilderte MC-Fragen aus dem schriftlichen Teil des M1 mit einem nicht parametrischen Test für ungepaarte Stichproben. Als Ergebnis waren keine signifikanten Unterschiede im Schwierigkeits- und Trennschärfeniveau zwischen bebilderten und nicht bebilderten MC-Fragen vorhanden, dasselbe ergab sich in einer nach MC-Frageformaten stratifizierten Analyse.
Wir schließen daraus, dass das bebilderte Itemformat für sich die Itemschwierigkeit nicht zu beeinflussen scheint. Die aktuellen Ergebnisse stimmen mit früheren retrospektiven Studien überein, die keine signifikanten Unterschiede zwischen Test- und Itemcharakteristika zwischen bebilderten und nicht bebilderten MC-Fragen zeigten.
Illustrated Multiple-choice questions (iMCQs) form an integral part of written tests in anatomy. In iMCQs, the written question refers to various types of figures, e. g. X-ray images, micrographs of histological sections, or drawings of anatomical structures. Since the inclusion of images in MCQs might affect item performance we compared characteristics of anatomical items tested with iMCQs and non-iMCQs in seven tests of anatomy courses and in two written parts of the first section of the German Medical Licensing Examination (M1).
In summary, we compared 25 iMCQs and 163 non-iMCQs from anatomy courses, and 27 iMCQs and 130 non-iMCQs from the written part of the M1 using a nonparametric test for unpaired samples. As a result, there were no significant differences in difficulty and discrimination levels between iMCQs and non-iMCQs, the same applied to an analysis stratified for MCQ formats.
We conclude that the illustrated item format by itself does not seem to affect item difficulty. The present results are consistent with previous retrospective studies which showed no significant differences of test or item characteristics between iMCQs and non-iMCQs.
Stem cell-based therapies require cells with a maximum regenerative capacity in order to support regeneration after tissue injury and organ failure. Optimization of this regenerative potential of mesenchymal stromal/stem cells (MSC) or their conditioned medium by in vitro preconditioning regimens are considered to be a promising strategy to improve the release of regenerative factors. In the present study, MSC were isolated from inguinal adipose tissue (mASC) from C57BL/6 mice, cultured, and characterized. Then, mASC were either preconditioned by incubation in a hypoxic environment (0.5% O2), or in normoxia in the presence of murine epidermal growth factor (EGF) or tumor necrosis factor α (TNFα) for 48 h. Protein expression was measured by a commercially available array. Selected factors were verified by PCR analysis. The expression of 83 out of 308 proteins (26.9%) assayed was found to be increased after preconditioning with TNFα, whereas the expression of 61 (19.8%) and 70 (22.7%) proteins was increased after incubation with EGF or in hypoxia, respectively. Furthermore, we showed the proliferation-promoting effects of the preconditioned culture supernatants on injured epithelial cells in vitro. Our findings indicate that each preconditioning regimen tested induced an individual expression profile with a wide variety of factors, including several growth factors and cytokines, and therefore may enhance the regenerative potential of mASC for cell-based therapies.
This paper presents three acceptability experiments investigating German verb-final clauses in order to explore possible sources of sentence complexity during human parsing. The point of departure was De Vries et al.'s (2011) generalization that sentences with three or more crossed or nested dependencies are too complex for being processed by the human parsing mechanism without difficulties. This generalization is partially based on findings from Bach et al. (1986) concerning the acceptability of complex verb clusters in German and Dutch. The first experiment tests this generalization by comparing two sentence types: (i) sentences with three nested dependencies within a single clause that contains three verbs in a complex verb cluster; (ii) sentences with four nested dependencies distributed across two embedded clauses, one center-embedded within the other, each containing a two-verb cluster. The results show that sentences with four nested dependencies are judged as acceptable as control sentences with only two nested dependencies, whereas sentences with three nested dependencies are judged as only marginally acceptable. This argues against De Vries et al.'s (2011) claim that the human parser can process no more than two nested dependencies. The results are used to refine the Verb-Cluster Complexity Hypothesis of Bader and Schmid (2009a). The second and the third experiment investigate sentences with four nested dependencies in more detail in order to explore alternative sources of sentence complexity: the number of predicted heads to be held in working memory (storage cost in terms of the Dependency Locality Theory [DLT], Gibson, 2000) and the length of the involved dependencies (integration cost in terms of the DLT). Experiment 2 investigates sentences for which storage cost and integration cost make conflicting predictions. The results show that storage cost outweighs integration cost. Experiment 3 shows that increasing integration cost in sentences with two degrees of center embedding leads to decreased acceptability. Taken together, the results argue in favor of a multifactorial account of the limitations on center embedding in natural languages.
HuR plays an important role in tumor cell survival mainly through posttranscriptional upregulation of prominent anti-apoptotic genes. In addition, HuR can inhibit the translation of pro-apoptotic factors as we could previously report for caspase-2. Here, we investigated the mechanisms of caspase-2 suppression by HuR and its contribution to chemotherapeutic drug resistance of colon carcinoma cells. In accordance with the significant drug-induced increase in cytoplasmic HuR abundance, doxorubicin and paclitaxel increased the interaction of cytoplasmic HuR with the 5ʹuntranslated region (5ʹUTR) of caspase-2 as shown by RNA pull down assay. Experiments with bicistronic reporter genes furthermore indicate the presence of an internal ribosome entry site (IRES) within the caspase-2-5ʹUTR. Luciferase activity was suppressed either by chemotherapeutic drugs or ectopic expression of HuR. IRES-driven luciferase activity was significantly increased upon siRNA-mediated knockdown of HuR implicating an inhibitory effect of HuR on caspase-2 translation which is further reinforced by chemotherapeutic drugs. Comparison of RNA-binding affinities of recombinant HuR to two fragments of the caspase-2-5ʹUTR by EMSA revealed a critical HuR-binding site residing between nucleotides 111 and 241 of caspase-2-5ʹUTR. Mapping of critical RNA binding domains within HuR revealed that a fusion of RNA recognition motif 2 (RRM2) plus the hinge region confers a full caspase-2-5ʹUTR-binding. Functionally, knockdown of HuR significantly increased the sensitivity of colon cancer cells to drug-induced apoptosis. Importantly, the apoptosis sensitizing effects by HuR knockdown were rescued after silencing of caspase-2. The negative caspase-2 regulation by HuR offers a novel therapeutic target for sensitizing colon carcinoma cells to drug-induced apoptosis.
Acetaminophen [paracetamol, N-acetyl-p-aminophenol (APAP)]-induced acute liver injury (ALI) not only remains a persistent clinical challenge but likewise stands out as well-characterized paradigmatic model of drug-induced liver damage. APAP intoxication associates with robust hepatic necroinflammation the role of which remains elusive with pathogenic but also pro-regenerative/-resolving functions being ascribed to leukocyte activation. Here, we shine a light on and put forward a unique role of the interleukin (IL)-1 family member IL-18 in experimental APAP-induced ALI. Indeed, amelioration of disease as previously observed in IL-18-deficient mice was further substantiated herein by application of the IL-18 opponent IL-18-binding protein (IL-18BPd:Fc) to wild-type mice. Data altogether emphasize crucial pathological action of this cytokine in APAP toxicity. Adding recombinant IL-22 to IL-18BPd:Fc further enhanced protection from liver injury. In contrast to IL-18, the role of prototypic pro-inflammatory IL-1 and tumor necrosis factor-α is controversially discussed with lack of effects or even protective action being repeatedly reported. A prominent detrimental function for IL-18 in APAP-induced ALI as proposed herein should relate to its pivotal role for hepatic expression of interferon-γ and Fas ligand, both of which aggravate APAP toxicity. As IL-18 serum levels increase in patients after APAP overdosing, targeting IL-18 may evolve as novel therapeutic option in those hard-to-treat patients where standard therapy with N-acetylcysteine is unsuccessful. Being a paradigmatic experimental model of ALI, current knowledge on ill-fated properties of IL-18 in APAP intoxication likewise emphasizes the potential of this cytokine to serve as therapeutic target in other entities of inflammatory liver diseases.
Gervais’ beaked whale Mesoplodon europaeus (Gervais, 1855) is restricted to the Atlantic Ocean. Although most records are from the North Atlantic, it is probably continuously distributed in deep warm waters around the equator (Mead 1989, Norman & Mead 2001). Its occurrence in West Africa is poorly known, as records are rare. It is classified as Data Deficient (Taylor et al. 2008).
Background: Rare diseases are, by definition, very serious and chronic diseases with a high negative impact on quality of life. Approximately 350 million people worldwide live with rare diseases. The resulting high disease burden triggers health information search, but helpful, high-quality, and up-to-date information is often hard to find. Therefore, the improvement of health information provision has been integrated in many national plans for rare diseases, discussing the telephone as one access option. In this context, this study examines the need for a telephone service offering information for people affected by rare diseases, their relatives, and physicians.
Methods: In total, 107 individuals participated in a qualitative interview study conducted in Germany. Sixty-eight individuals suffering from a rare disease or related to somebody with rare diseases and 39 health care professionals took part. Individual interviews were conducted using a standardized semi-structured questionnaire. Interviews were analysed using the qualitative content analysis, triangulating patients, relatives, and health care professionals. The fulfilment of qualitative data processing standards has been controlled for.
Results: Out of 68 patients and relatives and 39 physicians, 52 and 18, respectively, advocated for the establishment of a rare diseases telephone service. Interviewees expected a helpline to include expert staffing, personal contact, good availability, low technical barriers, medical and psychosocial topics of counselling, guidance in reducing information chaos, and referrals. Health care professionals highlighted the importance of medical topics of counselling—in particular, differential diagnostics—and referrals.
Conclusions: Therefore, the need for a national rare diseases helpline was confirmed in this study. Due to limited financial resources, existing offers should be adapted in a stepwise procedure in accordance with the identified attributes.
Die hier zu besprechende Monographie "Mensch und Landschaft im südwestlichen Latium in der römischen Antike" stellt die leicht überarbeitete Fassung der Dissertation von Michael Teichmann (im Folgenden T.) dar, die er im Winter 2016/17 an der Christian-Albrechts-Universität zu Kiel am Institut für Geoarchäologie eingereicht hat. Der Phoibos Verlag strebt mit der Serie "Phoibos Humanities Series" eine Doppelstrategie an und vertreibt das Werk sowohl als gedrucktes Buch (89 €) wie auch als E-Book (59 €). Möglicherweise erklärt sich so der Verzicht auf einen Index, da das maschinenlesbare E-Book einen solchen theoretisch überflüssig macht. Da der Rezensent mit dem gedruckten Buch gearbeitet hat, fiel das Fehlen eines Indexes doch negativ ins Gewicht. ...
Was war und ist heute die Rolle der Griots im alten Afrika? Es besteht darin, über das Leben der Gemeinschaft durch die verschiedenen historischen Begebenheiten zu berichten. So begreift auch Sembene Ousmane seine Bestimmung als Filmemacher. Er soll ein "Griot der modernen Zeiten sein". Diese Rolle als Vertreter der eignen Gemeinschaft in den modernen Medien, wie z. B. dem Kino, entspricht auch Djibril Diop Mambetys Auffassung, jenes Filmemachers aus dem Senegal, der den Film als revolutionäres Vehikel begreift. Aber was wäre der afrikanische Film, fragt sich Signer, hätte man nicht Regisseure wie Idriss Ouadreogo oder die regionale Institution des FESPACO, die jährlich Preise für afrikanische Filmemacher vergibt. Dies bedeutet, dass der afrikanische Film seit der Unabhängigkeit präsenter geworden ist und versucht, selber als Vehikel realer oder fiktionaler Faktenin Afrika zu sein. So verspricht es auch der 1988 gedrehte Film Camp "Thiaroye" von Sembene Ousmane und Thierno Faty Sow, der kolonialgeschichtliche Geschehnisse in Afrika möglichst authentisch zu erzählen.
Brachyplatys subaeneus (Westwood) (Hemiptera: Plataspidae) es una especie de chinche originaria de Asia que fue reportada en 2016 por primera vez en Panamá y las Américas. Dicha especie es un organismo invasor considerado como una plaga potencial para los cultivos de guandú (Cajanus cajan (L.) Huth) y otras leguminosas. Debido a que no se había trabajado más en este chinche desde su reporte, este estudio busca generar información respecto a su distribución geográfica en el país, focalizada a lo largo de la costa Pacífica de Panamá, desde Tortí, Panamá Este, hasta la región de Chitré, provincia de Herrera. A pesar de presentar esta distribución consideramos que esta especie invasora puede tener ámbitos de distribución más amplios en Panamá, tomando en cuenta el hecho de que es una especie con una alta tasa de reproducción y colonización.
Ulrich Gerhardt : Nachruf
(2018)
Background: Bradykinin-mediated angioedema (Bk-AE) can be life-threatening and requires specific targeted therapies. Knowledge of its epidemiology may help optimize its management.
Methods: We systematically searched the medical literature to identify abstracts of interest indexed between 1948 and March, 2016. We used published national survey data on the proportion of the population treated with angiotensin-converting enzyme inhibitors (ACEI) to derive estimates of the population prevalence of ACEI-AE in the USA, Germany and France. For hereditary angioedema (C1-INH-HAE) and C1-inhibitor related acquired angioedema (C1-INH-AAE), publications had to contain original epidemiologic data collection within a defined geographical area. Hereditary angioedema with normal C1-INH was not included in the analysis due to lack of clearly defined criteria.
Results: We identified 4 relevant publications on the prevalence of ACEI-AE, 6 on the prevalence of C1-INH-HAE, and 1 on the prevalence of C1-INH-AAE. The 1st year cumulative incidence of ACEI-AE was estimated to vary between 0.12 (population-based analyses) and 0.30 (meta-analyses of clinical trials) per 100 patient-years. The population prevalence of ACEI-AE was modeled to vary between 7 and 26 in 100,000. The prevalence of C1-INH-HAE was estimated to vary between 1.1 and 1.6 per 100,000. The prevalence of C1-INH-AAE was estimated to be 0.15 per 100,000 in one epidemiological investigation of AAE in Denmark.
Conclusions: Epidemiological evidence on Bk-AE is limited to North America and Europe. ACEI-AE is more common than C1-INH-HAE (~ 10:1), which is more common than C1-INH-AAE (~ 10:1). More studies are needed to comprehensively assess the epidemiological burden of Bk-AE.
How does social class affect people’s goals in social interactions? A rank-based perspective suggests actors from higher social classes (compared to lower social classes) have more agentic and less communal goals when interacting with same class or unspecified others. Focusing on targets’ social class, an identity-based perspective suggests the reverse: Actors should more strongly endorse communal (agentic) goals toward illegitimately lower class (higher class) compared to illegitimately higher class (lower class) targets, regardless of actors’ own social class. Three preregistered experiments (N = 2,023) manipulated actor’s social class and the nature of the target (illegitimately higher/lower class, same class, unspecified) and measured participants’ goals in imagined interactions using the Circumplex Scales of Intergroup Goals. The identity-based perspective received strong support: Across studies, actors expressed stronger agentic (communal) goals toward higher class (lower class) targets. The rank-based perspective received limited support, with relatively low-class (vs. relatively high-class) actors expressing stronger communal goals toward same-class targets.
This research investigated variation in the pronunciations of three RP vowels phonemes /e/, /ɜ:/ and /ə/, among Ewe speakers of English in Ghana. It focused on variation at both individual and societal levels, investigating how social relations within these structures influenced the use of the three vowels among the speakers. In this study, social structures were seen as a system where individual members depended on one another and were linked through multiple ties. The distribution of the vowels was in respect with the social variables: age, gender and education, including dialect and social network. The study used a corpus of word-list recorded in a face-to-face interview from 96 participants selected through stratification and networking across two dialect regions: Aŋlɔ and Eveme. Using both aural and acoustic analyses, coupled with ANOVA and t-test, the study has shown that the three RP vowels exist in Ghana Eve English as independent phonemes. Each of them however has allophonic variants; /e/ has variants [e̠], [ɪ] and [ɜ:]; /ɜ:/ has [eː] and [ɜ:], while /ə/ has [ə], [ɪ], [o] and [ʌ] as its variants. The choice of the variants of /ɜ:/ and /e/ have been found to depend on speaker age, gender, and social network. But the geographical location of the speaker will largely determine how these vowels are spoken. Phonological contexts as well as speaker idiosyncrasy are also likely to condition the choice of some of these variants, however, their effects seem less important as determinant of the differences observed than those of the social factors. It is evident that age, gender and class differentiations that have been widely reported cannot be universal, they can vary from one society to another. Also though social structures as well as social relations in a speech community can play significant roles in the individual’s linguistic repertoire, the attitude of the speaker and the phonological contexts of a segment can have a huge impact on the use of that variable.
Der Beitrag beschäftigt sich mit der Quellenlage zur Organisation der Bronzemetallurgie in West-, Süd- und Nordwestböhmen. In allen Regionen kommen Belege für den Herstellungsprozess während der gesamten Bronzezeit kontinuierlich vor. In Nordwestböhmen stammt die Mehrheit der Quellen aus der Urnenfelderzeit. Hier zeigen sich der gute Zugang zu den Rohstoffvorkommen (Zinn, Kupfer) im Erzgebirge/Krušné hory und die Beziehung zu den Flüssen Elbe/Labe und Eger/Ohře. Westböhmen bildet in der Bronzezeit ein Randgebiet mit nur wenigen metallurgischen Belegen, aber mit sehr guten Bezügen zu Zinn und Kupfer (vor allem im nördlichen Teil). In Südböhmen, wo der Schwerpunkt in der Frühbronzezeit (fast keine Funde aus Ha B) liegt, lassen sich die Kommunikationswege und Verbreitung entlang der Moldau/Vltava beobachten. Die Mehrheit der Produktionsorte fügt sich in das Siedlungsnetz ein und nutzte lokale Lagerstätten. Es konnten einige potenzielle Zentralorte der Metallurgie identifiziert werden. Allgemein überwiegen die Funde aus den Flachsiedlungen gegenüber den Höhensiedlungen (vor allem in Nordwestböhmen). Es gibt folglich keine ausschließliche Beziehung der Bronzemetallurgie zu den Burgwällen, womit Vorstellungen, die Elite organisiere die Bronzemetallurgie, widerlegt werden. Die Organisation der bronzezeitlichen Metallurgie war sicher komplexer.
Although there are many dialect speakers in Bavaria, the dialect - mainly because of its non-standardized spelling - is usually not used in common print media or on nationwide television. Nevertheless, the Bavarian dialect appears on Bavarian television (BR) and in cinema films. However, the Bavarian used on television or in films is frequently not a genuine dialect; instead it is a synthetic language which resembles the German standard and merely refers to the dialect. This is mainly due to the needs of non-dialect speakers, who would definitely have comprehension problems with the genuine dialect. Furthermore, the Bavarian dialect is often used on online platforms, such as Facebook or YouTube. In these conversational situations, face-to-face communication is replaced by written texts. In the case of dialect speakers, these texts can appear as written dialect; due to the non-standardized spelling, the texts are strongly individualized.
α-ketoglutarate dehydrogenase inhibition counteracts breast cancer-associated lung metastasis
(2018)
Metastasis formation requires active energy production and is regulated at multiple levels by mitochondrial metabolism. The hyperactive metabolism of cancer cells supports their extreme adaptability and plasticity and facilitates resistance to common anticancer therapies. In spite the potential relevance of a metastasis metabolic control therapy, so far, limited experience is available in this direction. Here, we evaluated the effect of the recently described α-ketoglutarate dehydrogenase (KGDH) inhibitor, (S)-2-[(2,6-dichlorobenzoyl) amino] succinic acid (AA6), in an orthotopic mouse model of breast cancer 4T1 and in other human breast cancer cell lines. In all conditions, AA6 altered Krebs cycle causing intracellular α-ketoglutarate (α-KG) accumulation. Consequently, the activity of the α-KG-dependent epigenetic enzymes, including the DNA demethylation ten-eleven translocation translocation hydroxylases (TETs), was increased. In mice, AA6 injection reduced metastasis formation and increased 5hmC levels in primary tumours. Moreover, in vitro and in vivo treatment with AA6 determined an α-KG accumulation paralleled by an enhanced production of nitric oxide (NO). This epigenetically remodelled metabolic environment efficiently counteracted the initiating steps of tumour invasion inhibiting the epithelial-to-mesenchymal transition (EMT). Mechanistically, AA6 treatment could be linked to upregulation of the NO-sensitive anti-metastatic miRNA 200 family and down-modulation of EMT-associated transcription factor Zeb1 and its CtBP1 cofactor. This scenario led to a decrease of the matrix metalloproteinase 3 (MMP3) and to an impairment of 4T1 aggressiveness. Overall, our data suggest that AA6 determines an α-KG-dependent epigenetic regulation of the TET–miR200–Zeb1/CtBP1–MMP3 axis providing an anti-metastatic effect in a mouse model of breast cancer-associated metastasis.
Three Neotropical species are transferred to the genus Premnobius Eichhoff (Coleoptera: Curculionidae: Scolytinae: Ipini): Premnobius assiduus (Schedl, 1961, from Xyleborus), P. flechtmanni (Wood, 2007, from Acanthotomicus) and P. neoajunctus (Schedl, 1967, from Xyleborus). An illustrated key is presented for the native and introduced species of the genus known from the New World.
Two new species of marine Platyhelminthes, Microstomum laurae sp. nov. and Microstomum edmondi sp. nov. (Macrostomida: Microstomidae) are described from the west coast of Sweden. Microstomum laurae sp. nov. is distinguished by the following combination of characters: rounded anterior and posterior ends; presence of approximately 20 adhesive papillae on the posterior rim; paired lateral red eyespots located level with the brain; preoral gut extending anterior to brain and and very small sensory pits. Microstomum edmondi sp. nov. is a protandrous hermaphrodite with a single ovary, single testis and male copulatory organ with stylet. It is characterized by a conical pointed anterior end, a blunt posterior end with numerous adhesive papillae along the rim, and large ciliary pits. The stylet is shaped as a narrow funnel with a short, arched tip. In addition, the first records of fully mature specimens of Microstomum rubromaculatum von Graff, 1882 from Fiskebäckskil and a phylogenetic analysis of Microstomum Schmidt, 1848 based on the mitochondrial cytochrome oxidase I (COI) gene are presented.
Quasifree one-proton knockout reactions have been employed in inverse kinematics for a systematic study of the structure of stable and exotic oxygen isotopes at the R3B/LAND setup with incident beam energies in the range of 300–450 MeV/u. The oxygen isotopic chain offers a large variation of separation energies that allows for a quantitative understanding of single-particle strength with changing isospin asymmetry. Quasifree knockout reactions provide a complementary approach to intermediate-energy one-nucleon removal reactions. Inclusive cross sections for quasifree knockout reactions of the type AO(p,2p)A−1N have been determined and compared to calculations based on the eikonal reaction theory. The reduction factors for the single-particle strength with respect to the independent-particle model were obtained and compared to state-of-the-art ab initio predictions. The results do not show any significant dependence on proton-neutron asymmetry.
Wie kommen Objekte ins Museum? Wurden sie gekauft, gesammelt, geerbt oder sogar geraubt? Mit diesen grundlegenden Fragen beschäftigt sich die Provenienzforschung nicht erst seit dem aufsehenerregenden Bilderfund in München 2013, sondern sie dienen auch vier Frankfurter Museen als verbindendes Element ihres Kooperationsprojektes Gekauft. Gesammelt. Geraubt. Vom Weg der Dinge ins Museum. ...
"Eames-the architect and the painter" ist ein Dokumentarfilm über das Paar Ray und Charles Eames, der sowohl ihr Arbeits-, als auch ihr Privatleben vorstellt. Der Film erzählt über die sehr eindrucksvolle Schaffenskraft und Arbeitsweise des kreativen Paares, das in seiner Werkstatt, dem Design Office Eames, ab Mitte der 1940er Jahre vor allem eine neue, moderne Formensprachen für Möbel suchte. Ihr Hauptanliegen galt von Beginn an der seriellen Anfertigung von Stühlen und Möbeln, die den neuen Ansprüchen des nach Aufbruch strebenden Zeitgeistes gerecht werden sollten. Dementsprechend wichtig war es ihnen, einen Ort zu etablieren, in dem, fern jeglicher Dogmatik und gängiger Arbeitsweisen, experimentell und freigeistig gearbeitet werden konnte. ...
This paper presents a new account of the generalization that focused elements cannot be elided, framed within Unalternative Semantics, a framework that does away with syntactic F-marking. We propose the mirror image of the generalization: what is elided cannot introduce alternatives. We implement this as a focus restriction in UAS and then go on to show how to account for MAXELIDE effects using the same technique, without making reference to any transderivational constraints.
Von Passivität, Abneigung, gar einem "tief verwurzelte[n] Mißtrauen" gegenüber dem Interview, wie es Volkmar Hansen als typisch für Schriftstellerinnen und Schriftsteller diagnostiziert, kann im Falle Peter Kurzecks keine Rede sein. Der Autor zeigt sich in journalistischen Gesprächen deutlich engagiert, er gibt bemerkenswert ausführlich Auskunft: über den Inhalt seiner Romane, den Prozess des Schreibens und dessen Motivation; über die Erinnerung an die eigene Kindheit im hessischen Staufenberg und die Flucht aus Westböhmen dorthin; über bereits geschriebene oder noch zu schreibende Bücher, über Möglichkeiten und Grenzen der eigenen autobiographisch grundierten Erinnerungsarbeit. Wo andere mit Abneigung reagieren und ausweichen, legt Kurzeck sein Schreiben bereitwillig offen, um dabei eben nicht nur zu erläutern, worum es in den Texten seiner "Serie" inhaltlich, motivisch oder konzeptionell geht oder gehen wird, sondern auch, um dezidiert Einblicke in die eigene Dichterwerkstatt zu ermöglichen.
Wenn es die Aufgabe einer Ikonologie der Architektur ist, das Verstehen "des Bauwerks als Sinnträger" zu befördern, unter anderem also die Frage zu beantworten, was "den Menschen [...] diese oder jene Form bedeutet" hat, dann kann versuchsweise 'Monumentalität' ein Suchbegriff sein, der geeignet ist, der ikonologischen Bedeutung von Bauten näher auf die Spur zu kommen. Denn hier geht es um symbolische Aufladung, die etwas entstehen lässt, das Martin Warnke einmal "Bedeutungsarchitektur" nannte. Doch der Begriff ist belastet. Historisch galt Monumentalität in der Architektur schon nach dem Ersten Weltkrieg und den Exzessen des Historismus als obsolet; die Klassische Moderne zentrierte sich um ganz andere Begriffe wie den der Funktion. Monumentalität als Phänomen schien verschwunden, und der Funktionalismus brauchte keine Ikonologie. Nur so exotische Projekte wie das Neu-Delhi von Edwin Lutyens und später die unsäglichen Monumentalbauten der europäischen Diktaturen waren noch monumental. Doch plötzlich wurde an unerwarteter Stelle, nämlich aus dem Zentrum der modernen Bewegung selbst, deren Protagonisten im Lauf der 1930er Jahre aus politischen Gründen vielfach in die USA emigriert waren, und zudem zu einem auf den ersten Blick irritierenden Zeitpunkt die Diskussion neu eröffnet. Niemand Geringeres nämlich als Sigfried Giedion, der Chefideologe der Moderne, startete einen entsprechenden Vorstoß. Zusammen mit José Luis Sert und Fernand Léger verfasste er 1943 seine 'Nine Points on Monumentality'.
The Gleason grading system remains the most powerful prognostic predictor for patients with prostate cancer since the 1960s. Its application requires highly-trained pathologists, is tedious and yet suffers from limited inter-pathologist reproducibility, especially for the intermediate Gleason score 7. Automated annotation procedures constitute a viable solution to remedy these limitations. In this study, we present a deep learning approach for automated Gleason grading of prostate cancer tissue microarrays with Hematoxylin and Eosin (H&E) staining. Our system was trained using detailed Gleason annotations on a discovery cohort of 641 patients and was then evaluated on an independent test cohort of 245 patients annotated by two pathologists. On the test cohort, the inter-annotator agreements between the model and each pathologist, quantified via Cohen’s quadratic kappa statistic, were 0.75 and 0.71 respectively, comparable with the inter-pathologist agreement (kappa = 0.71). Furthermore, the model’s Gleason score assignments achieved pathology expert-level stratification of patients into prognostically distinct groups, on the basis of disease-specific survival data available for the test cohort. Overall, our study shows promising results regarding the applicability of deep learning-based solutions towards more objective and reproducible prostate cancer grading, especially for cases with heterogeneous Gleason patterns.
Das Ziel der vorliegenden Arbeit war es, MALDI-Massenspektrometrie als robuste Analysenmethode für die quantitative Analyse niedermolekularer Verbindungen aus komplexen biologischen Matrizes zu etablieren. Zu Beginn der Arbeit wurden drei typische Fragestellungen im Bereich der Lebensmittelanalytik, der medizinischen Forschung und der klinischen Chemie ausgewählt, um die Methodik anhand dieser Modellsysteme zielgerichtet zu entwickeln und zu bewerten. Für jede dieser Fragestellungen wird routinemäßig ein hoher Probendurchsatz verlangt und damit werden hohe Anforderungen an die Probenvorbereitung gestellt, da diese einfach, schnell, reproduzierbar, Matrix-tolerant und automatisierbar sein muss um die Weiterentwicklung zur Hochdurchsatzanalytik zu erlauben.
Der quantitative Nachweis von Melamin und seinen Derivaten wurde aufgrund des Aufkommens von Milchprodukten, die mit diesen Verbindungen kontaminiert waren, ein wichtiger Bestandteil der Analytik dieser Lebensmittel. Insbesondere an diesem Beispiel zeigte sich der Vorteil des Einsatzes von MALDI-Massenspektrometrie zur Analyse kleiner Moleküle. Aufgrund der höheren Toleranz gegenüber Puffern und Salzen konnte die Probenvorbereitungszeit der für die FDA entwickelten Methode zur Quantifizierung von Melamin in Milchpulver mittels LC-ESI von ca. 140 min auf 90 min reduziert werden, da auf die zeitaufwendige Flüssigchromatographie verzichtet werden konnte. So wurde Melamin mit einem LLOQ von 0,5 ppm quantifiziert, was unterhalb der Vorgaben der WHO (2,5 ppm in Milichpulver und 1 ppm in Babynahrung) lag. Cyanursäure, ein Derivat von Melamin welches für die Bildung schwerlöslicher Komplexe in der Niere mitverantwortlich gemacht wird, konnte ebenfalls mit der entwickelten MALDI-MS Methode quantifiziert werden. Allerdings war die ermittelte Bestimmungsgrenze mit 15 ppm um den Faktor 30 schlechter als bei Melamin. Die Nachweisgrenze bei MALDI-MS ist stark von der MALDI-Matrix abhängig und die Verwendung von Sinapinsäure war eine gute Kompromisslösung, um die Analyten in einem Spot im positiven und negativen Reflektormodus zu analysieren. Allerdings wurde diese Matrix zur Analyse von Analyten im positiven Reflektormodus entwickelt. Bislang wurden nur wenige Matrizes für MALDI-MS im negativen Reflektormodus beschrieben, um z.B. Säuren besser nachweisen zu können. Forschung in diesem Bereich wird neue Möglichkeiten zur Detektion negativ geladener kleiner Moleküle ergeben.
Des Weiteren wurden im Rahmen dieser Arbeit auch Lösungen für klinische Fragestellungen wie etwa den Nachweis von Methylphenidat im Plasma und Gehirn von Ratten oder der Dried Blood Spot Analytik entwickelt. Bei beiden Methoden wurde jeweils nur eine einfache Flüssig-Flüssig-Extraktion zur Probenvorbereitung angewendet und sie ließen sich sehr gut auf Realproben übertragen.
Methylphenidat konnte im Plasma im Konzentrationsbereich von 0,1-40 ng/mL und im Hirnhomogenat im Konzentrationsbereich von 0,4-40 ng/mL quantifiziert werden, was gut im Konzentrationsbereich der Realproben von mit Methylphenidat gefütterten Ratten lag. Dazu standen das Plasma und die Gehirne von fünf Ratten zur Verfügung. Es wurde eine lineare Korrelation zwischen der MPH-Konzentration im Gehirnhomogenat und im Plasma gefunden, was basierend auf den bis dato bekannten Literaturergebnissen ein zu erwartendes Ergebnis war, aber zukünftig mit einer größeren Anzahl von Versuchstieren verifiziert werden sollte. Während der Methodenentwicklung war auch bei diesem Projekt die Auswahl der MALDI-Matrix ausschlaggebend für den Erfolg der Messungen. Im MALDI-Massenspektrum interferierte das Signal des Natriumaddukts von CHCA mit dem Signal von MPH. Für dieses Problem kamen zwei mögliche Lösungen in Betracht. Erstens die Quantifizierung mit ClCCA als MALDI-Matrix, da hier keine Interferenzen auftraten. In ersten Vorversuchen konnte MPH so in einem Konzentrationsbereich von 1-48 ng/mL mit einer exzellenten Linearität von R2=0,9992 quantifiziert werden. Eine zweite mögliche Problemlösung war die Verwendung von Tandem-Massenspektrometrie. Hierzu wurden Fragmentionen-Massenspektren der überlagerten Signale aufgenommen. MPH und der verwendete interne Standard MPH-d9 zeigten dabei spezifische Fragmentionensignale, über die quantifiziert wurde. Da die Sensitivität um den Faktor 100 im Vergleich zu MS-Spektren von CHCA und ClCCA gesteigert werden konnte, wurde die weitere Methodenentwicklung basierend auf der Tandem-Massenspektrometrie mit der MALDI-Matrix CHCA durchgeführt. Überdies sind MS/MS-Versuche unter Verwendung von ClCCA als MALDI-Matrix für kleine Moleküle sehr erfolgsversprechend und sollten in weiteren Forschungsarbeiten durchgeführt werden.
Die Dried Blood Spot Technik als alternative Probenvorbereitung bietet eine Reihe von Vorteilen, wie etwa den einer einfacheren Lagerung und eines einfacheren Transports einer großen Menge von Proben. Darüber hinaus werden nur wenige Mikroliter Blut verwendet, was vorteilhaft ist bei z B. klinischen Studien oder dem Therapeutic Drug Monitoring. Diese Art der Probennahme ist somit eine perfekte Ergänzung für weitere quantitative Analysen von Methylphenidat in Rattenblut. Den Ratten würden nur wenige Mikroliter Blut entnommen werden, was ihr Überleben sichert und der Transport der Proben auf dem Postweg wäre wesentlich einfacher. Um eine allgemein verwendbare DBS-MALDI-MS-Methode zu entwickeln, wurden neben Methylphenidat auch bekannte Analyten aus dem Bereich des Dopings sowie Lamotrigin, Coffein und Theophyllin als Beispiele für das Therapeutic Drug Monitoring verwendet. Es wurden verschiedene Lösungsmittel zur Extraktion eingesetzt, wobei sich eine Kombination aus Methyl-tert-Butylether und Ethanol, sowie Aceton als am besten geeignet erwies. Einige Analyten wie Coffein, Theophyllin und Lamotrigin wurden bis zu einer Konzentration von 0,5 μg/mL quantifiziert. Diese Bestimmungsgrenze ist bei Analyten aus dem Bereich des Dopings wie z.B. Salbutamol, Methylphenidat oder Clenbuterol, deren therapeutisch wirksame Plasmakonzentration im Bereich von wenigen Nanogramm pro Milliliter Blut liegt, um den Faktor 15-500 zu hoch. Diese Analyten waren bis zu einer Konzentration von 5 μg/mL im Blut mittels MALDI-MS problemlos nachweisbar. Um die Sensitivität zu erhöhen, ist es allerdings sinnvoll, die Extraktion zukünftig für die einzelnen Analyten zu optimieren, sie mittels Festphasenextraktion oder LC anzureichern und MS/MS-Spektren aufzunehmen. Für die Analyten Coffein, Theophyllin und Lamotrigin, deren therapeutisch wirksame Plasmakonzentration im ein- bis zweistelligen Mikrogramm-pro-Milliliter Bereich liegt, eignete sich die entwickelte Methode sehr gut. Es wurde eine Methodenvalidierung durchgeführt, wobei die validierten Parameter den Vorgaben der FDA entsprachen.
Da die Auswahl der MALDI-Matrix bei den verschiedenen Methodenentwicklungen jeweils ein kritischer Faktor war, wurden abschließend eine Auswahl von Analyten mit einer Molekülmasse bis ca. 600 Da mit verschiedenen MALDI-Matrizes präpariert. Ein Großteil der Analyten wurde am sensitivsten mit ClCCA nachgewiesen. Im Rahmen dieser Versuche wurde auch erstmals ein Strukturanalogon von ClCCA, und zwar ClCCA-Tetrazol, als alternative MALDI-Matrix eingesetzt, bei welchem die Carboxylgruppe durch einen Tetrazolring ausgetauscht wurde. Diese zeigte eine sehr homogene Kristallisation und für einige Analyten eine bis zu Faktor 3 höhere Signalintensität im Vergleich zu ClCCA. Außerdem war auffällig, dass einige Analyten unter bestimmten Präparationsbedingungen wie z B. der Graphite Supported Preparation sensitiver mittels MALDI-MS nachweisbar waren. Bei anderen Analyten verschlechterten sich die Analysenergebnisse. Graphit verändert stark die Kristallisation der MALDI-Matrix und es wird vermutet, dass sich dies auf den Einbau der Analyten in die Matrixkristalle auswirkt. Es konnte bislang aber noch nicht abschließend geklärt werden, wie genau die Präparation der Proben Einfluss auf den Einbau der Analyten in die Matrix nimmt. Eine Untersuchung dieser Phänomene sollte daher Gegenstand weiterer Forschungsprojekte sein.
Zusammenfassend stellt die MALDI-Massenspektrometrie eine schnelle und robuste Methode zur Quantifizierung einer Vielzahl kleiner Moleküle in komplexen biologischen Matrizes dar.
Dialektik
(2018)
Was 'Dialektik' nun genau sei, darüber gibt es immer noch sehr verschiedene und auch einander ausschließende Auffassungen. Vor allem auch darüber, ob es eine Dialektik gebe oder geben könne, die sich noch besonders durch das Attribut 'materialistisch' empfehlen würde. Je näher wir hinsehen, desto mehr entschwindet uns der Begriff, der einmal so viele Gewissheiten trug. Vielleicht liegt das auch schon daran, dass sich im Begriff der Dialektik viele Bedeutungsdimensionen gleichsam sedimentiert haben; er trägt schwer an seiner Geschichte und kann sich gerade deshalb immer wieder von einseitigen Fixierungen zurückziehen.
The Trichoptera of Panama V. Descriptions of new species, new country records, and a synonymy
(2018)
The Río Chiriqui basin is one of 52 major watershed areas, or cuencas, in the Republic of Panama. It occurs in western Panama, discharges into the Pacific Ocean, and includes portions of Volcán Barú on its northern extent. The Río Caldera occupies the northernmost subbasin of this basin. Two of its tributaries, Quebrada Grande and Quebrada Jaramillo, occur in close proximity and on opposite sides, and have different recent geologic histories and current land use patterns. During the course of investigating the caddisfly fauna of these two drainages, three new species of the microcaddisfly genus Neotrichia Morton (Trichoptera: Hydroptilidae) were identified: N. collierorum and N. anzuelo from Quebrada Jaramillo and N. tatianae from Quebrada Grande. These are described and figured herein. We also add one new genus (Rhyacopsyche Mueller) and five new country records (Hydroptila paschia Mosely, Metrichia ancora Bueno-Soria and Holzenthal, Ochrotrichia jolandae BuenoSoria and Holzenthal, Rhyacopsyche obliqua Flint, and Chimarra (Curgia) maritza Flint) for Panama. Finally, we designate Ochrotrichia abrelata Harris and Armitage, 2015 as a junior synonym of Ochrotrichia jolandae Bueno-Soria and Holzenthal, 2008. This synonymy and the newly recorded species and country records increase Panama’s known trichopteran fauna to 350 species, distributed among 15 families and 52 genera.
The Republic of Panama currently has 358 recorded species of Trichoptera. Herein we add 25 new country records for Panama. The newly recorded taxa increase Panama’s total known caddisfly fauna to 383 species, distributed among 15 families and 52 genera. These results are part of an ongoing effort to characterize the caddisfly fauna of Panama, and to evaluate that country’s major watersheds (cuencas).
Background: Understanding the location and cell-type specific binding of Transcription Factors (TFs) is important in the study of gene regulation. Computational prediction of TF binding sites is challenging, because TFs often bind only to short DNA motifs and cell-type specific co-factors may work together with the same TF to determine binding. Here, we consider the problem of learning a general model for the prediction of TF binding using DNase1-seq data and TF motif description in form of position specific energy matrices (PSEMs).
Methods: We use TF ChIP-seq data as a gold-standard for model training and evaluation. Our contribution is a novel ensemble learning approach using random forest classifiers. In the context of the ENCODE-DREAM in vivo TF binding site prediction challenge we consider different learning setups.
Results: Our results indicate that the ensemble learning approach is able to better generalize across tissues and cell-types compared to individual tissue-specific classifiers or a classifier applied to the data aggregated across tissues. Furthermore, we show that incorporating DNase1-seq peaks is essential to reduce the false positive rate of TF binding predictions compared to considering the raw DNase1 signal.
Conclusions: Analysis of important features reveals that the models preferentially select motifs of other TFs that are close interaction partners in existing protein protein-interaction networks. Code generated in the scope of this project is available on GitHub: https://github.com/SchulzLab/TFAnalysis (DOI: 10.5281/zenodo.1409697)
Background: Bidirectional promoters (BPs) are prevalent in eukaryotic genomes. However, it is poorly understood how the cell integrates different epigenomic information, such as transcription factor (TF) binding and chromatin marks, to drive gene expression at BPs. Single-cell sequencing technologies are revolutionizing the field of genome biology. Therefore, this study focuses on the integration of single-cell RNA-seq data with bulk ChIP-seq and other epigenetics data, for which single-cell technologies are not yet established, in the context of BPs.
Results: We performed integrative analyses of novel human single-cell RNA-seq (scRNA-seq) data with bulk ChIP-seq and other epigenetics data. scRNA-seq data revealed distinct transcription states of BPs that were previously not recognized. We find associations between these transcription states to distinct patterns in structural gene features, DNA accessibility, histone modification, DNA methylation and TF binding profiles.
Conclusions: Our results suggest that a complex interplay of all of these elements is required to achieve BP-specific transcriptional output in this specialized promoter configuration. Further, our study implies that novel statistical methods can be developed to deconvolute masked subpopulations of cells measured with different bulk epigenomic assays using scRNA-seq data.
O presente artigo tem como objetivo analisar a construção de imagens discursivas de aprendizes em sumários e em atividades contidas em livros didáticos de Alemão como Língua Estrangeira (ALE), e de que modo essas construções antecipam que tipo de inserção esse aprendiz teria de/poderia ocupar nessa comunidade de produção/circulação de textos na língua alvo. Nesse sentido, o quadro teórico se constrói a partir da articulação entre a perspectiva polifônica da linguagem (BAKHTIN 2011), a noção de práticas discursivas (FOUCAULT 2004; MAINGUENEAU 2008) e o disciplinamento de saberes (FOUCAULT 2002), considerando a relevância de tal articulação para uma crítica à Linguística Aplicada a partir de Rocha e Daher (2015). Por meio das análises de livros didáticos de ALE, observamos a construção de imagens de aprendiz que parece retirá-lo das situações de interação, considerando-o mero espectador, que se ocupará de repetir sentenças e estruturas determinadas por uma simulação artificial de situações comunicativas, mais do que permitir a ele espaços de interação e de inserção nessas situações. Além disso, os materiais comunicam uma imagem de aprendiz-consumidor-turista, interessado em aprender a língua para fazer viagens, realidade essa distante da brasileira.
Dieser Aufsatz widmet sich den Problemen der "Medienphilosophie", die vor allem vom gerade erschienenen Handbuch der Medienphilosophie in aller Schärfe aufgeworfen wurden – auch vom Autor dieser Zeilen, der selbst mit einem Beitrag im Buch vertreten ist. Er ist so etwas wie der Versuch einer Klärung der Probleme, die sich in den letzten 50 Jahren in den Medien angesammelt haben.
Poetic encounter: Rhapsodies from the South is compilation of poems by Southern African Writers from South Africa and Zimbabwe. The poems, were written not only to depict life but also tell tales of socio-political and economic history that Southern African people traversed from colonialism, apartheid to freedom. Therefore, readers from all walks-of-life can identify with themes such as apartheid, economic deprivation, religion and culture, love and so forth that are carefully ensconced in this compilation. The authors invite the readers, to not only indulge the lived injustice and violent nature of both our historic past and trajectory to the current state of affairs, but also appreciate, cry, smile and reminiscence about the life in general as encapsulated in this refreshing and aesthetic work of art - the poetic encounter.
Neurons collect their inputs from other neurons by sending out arborized dendritic structures. However, the relationship between the shape of dendrites and the precise organization of synaptic inputs in the neural tissue remains unclear. Inputs could be distributed in tight clusters, entirely randomly or else in a regular grid-like manner. Here, we analyze dendritic branching structures using a regularity index R, based on average nearest neighbor distances between branch and termination points, characterizing their spatial distribution. We find that the distributions of these points depend strongly on cell types, indicating possible fundamental differences in synaptic input organization. Moreover, R is independent of cell size and we find that it is only weakly correlated with other branching statistics, suggesting that it might reflect features of dendritic morphology that are not captured by commonly studied branching statistics. We then use morphological models based on optimal wiring principles to study the relation between input distributions and dendritic branching structures. Using our models, we find that branch point distributions correlate more closely with the input distributions while termination points in dendrites are generally spread out more randomly with a close to uniform distribution. We validate these model predictions with connectome data. Finally, we find that in spatial input distributions with increasing regularity, characteristic scaling relationships between branching features are altered significantly. In summary, we conclude that local statistics of input distributions and dendrite morphology depend on each other leading to potentially cell type specific branching features.
Landwirtschaft ist der Hauptmotor der westafrikanischen Wirtschaft und Kleinbauern liefern fast 70 % des Nahrungsmittelbedarfs. Traditionell wird hauptsächlich Regenfeldbau betrieben, der durch geringen Agrarinput und die Nutzung von einfachen Werkzeugen wie Hacke und Buschmesser gekennzeichnet ist. Die Ernteerträge sind gering und die Bodenfruchtbarkeit sinkt schnell nach einigen Anbaujahren. Infolgedessen werden Wald- und Weidefläche gerodet und die Landdegradation wird beschleunigt. Dies hat direkte Auswirkungen auf die landwirtschaftliche Produktivität und die Ernährungssicherheit der Kleinbauern.
Die vorliegende Arbeit hat sich das Ziel gesetzt, sozio-ökonomische und geo-ökologische Faktoren, die den Landnutzungswandel in zwei Agrarökosystemen der Atakora Gebirgskette steuern, aufzudecken. Schließlich sollen ortsangepasste Maßnahmen vorgeschlagen werden, um die Agrarökosysteme wiederherzustellen und ihre Dienstleistungen für Kleinbauern zu erhalten.
Haushaltsbefragungen und Gruppendiskussionen wurden während Geländeaufenthalten in den Jahren 2014 und 2015 in den Dörfern der beiden Ethnien durchgeführt. Die Landnutzung und ihr Wandel werden über knapp 30 Jahre anhand von Bildern des Satellitensystems LANDSAT aus den Jahren 1987, 2001 und 2015 ausgewertet. Eine überwachte Klassifikation nach dem „Maximum Likelihood“-Klassifkationsalgorithmus und Veränderungs-analysen wurden durchgeführt. Zum Erfassen der Variabilität der Agrarparameter der Böden wurden Bodenprofile nach dem Catena-Prinzip gegraben. Bodenproben wurden aus jedem Horizont genommen. Anschließend wurden einige physische Parameter und die Nährstoffgehalte vom Fachpersonal des bodenkundlichen Labors des Instituts für Physische Geographie (Geowissenschaften) bestimmt.
Innerhalb der knapp letzten dreißig Jahre (1987-2015) ist die natürliche Vegetation bei den beiden Ethnien zugunsten der Landwirtschaft und der bebauten bzw. vegetationsfreien Flächen zurückgegangen. Über die analysierten Zeiträume liegen mehr Flächen bei den Ditamari (47,24%) unter einer negativen Dynamik als bei den Éwé (36,41%). Die Untersuchung der Steuerungsfaktoren des Landnutzungswandels bringt heraus, dass der höhere Anteil an positiv veränderten Flächen bei den Éwé ist nicht durch bessere Landnutzungsstrategien begründet. Vielmehr stellt das Relief der begrenzende Faktor für die Ausdehnung der Ackerflächen und damit die bessere Erhaltung der natürlichen Vegetation bei den Éwé dar.
Die erste Annahme, dass Veränderungen in der Landnutzung die Landdegradation zur Folge haben, wird in den beiden Untersuchungsgebieten bestätigt. Die abnehmende Dichte der Vegetationsdecke begünstigt Prozesse der Flächen-, Rillen- und Rinnenspülung. Zudem werden die ökologischen Bodenfunktionen vermindert. Erscheinungen der Landdegradation bei den Ditamari sind die Ausdehnung von oberflächlich verkrusteten Arealen und die Verbreitung des Unkrautes Striga hermontica. Bei den Éwés tritt eine starke Profilverkürzung der Böden ein und das anstehende Gestein wird an mehreren Stellen freigelegt.
Die zweite Hypothese wird in Hinsicht auf die räumliche und ethnische Differenzierung der Folgen der Landdegradation bestätigt. Allerdings sind nicht, wie vermutet, die Ditamari verletzbarer als die Éwés. Die beiden Ethnien betreiben eine intensive Subsistenzwirtschaft und die Éwé entwickeln weniger Anpassungsstrategien als die Ditamari. Im Hinblick auf die globale Erwärmung könnte die Landdegradation in den beiden Gebieten fortschreiten und die Folgen auf der Landschaft und den Kleinbauern verschärfen. Die Éwé wären, anders als vermutet, verletzbarer als die Ditamari. Eine Fortschreitung der Landdegradation könnte bei den Kleinbauern Éwés langfristig den Zusammenbruch des Agrarökosystemen hervorrufen. Sie könnten langfristig die Grundlage ihrer Existenzsicherung verlieren.
Die Studie zeigt auf, dass traditionell, zurückgezogen lebende Völker wie die Ditamari das Agrarökosystem nachhaltiger bewirtschaften und angesichts der Landdegradation anpassungsfähiger sind als tief umgewandelte Gesellschaften wie die Éwés. Sie bringt heraus, dass Kleinbauern Westafrikas keinesfalls als eine Einheit betrachtet werden sollten. Jede Ethnie ist durch Merkmale gekennzeichnet, die ihre Gestaltung der Landschaft beeinflussen. Diese Vielfältigkeit und Besonderheiten der kleinbäuerlichen Gesellschaften müssen in der Entwicklungszusammenarbeit stärker berücksichtigt werden.
Im Naturschutzgebiet „Kühkopf-Knoblochsaue“ in der hessischen Rheinaue wurden 2013 121 dreijährige Pflanzen der Wilden Weinrebe in zwei Bereichen der Kühkopfaue angepflanzt. Für diese Anpflanzung standen 65 Genotypen zur Verfügung. 2014 überlebten 86 % der Pflanzen, 79 % wurden als „gut“ oder „durchschnittlich“ bonitiert.
Im 19. und 20. Jahrhundert war Georgien mit Ausnahme der Jahre der kurzlebigen Georgischen Demokratischen Republik (1918–1921) Bestandteil des russischen und später des sowjetischen Imperiums. Als Gegenstand von Hegemonialkämpfen zwischen Nationen und Imperien wurde der politische Raum des georgischen Feudalkönigreiches und der geographische Raum zwischen dem Kaukasus und dem Schwarzen Meer seit der Antike immer wieder symbolisch und affektiv aufgeladen, gedeutet und umgedeutet. Diese Kollektivmonographie rekonstruiert die Wechselwirkung geopoetischer und geopolitischer Verschiebungen seit dem ausgehenden 18. Jahrhundert, die Erfindung des Kaukasus als eines einheitlichen geokulturellen Raumes, die kulturelle Semantisierung des Schwarzen Meeres und der Kolchis erstmalig als einen Dialog zwischen georgischen, abchasischen und russischen Perspektiven.
2018 ist Georgien Ehrengast der Frankfurter Buchmesse. Zum ersten Mal nach der Wende wird die georgische Literatur damit prominent in einer fremden Sprache präsentiert. Gerade die Literaturen kleiner Nationen sind auf internationale Anerkennung dieser Art besonders angewiesen. Doch gibt es einen qualitativen Unterschied zwischen Literaturen 'kleiner' und 'großer Nationen'? Diese Frage ist im Spannungsfeld zweier Konzepte zu diskutieren, die mit dem der Nationalliteratur als lange dominierendem Ordnungsprinzip literarischer Texte konkurrieren: kleine Literatur und Weltliteratur.
The genus of Neotropical frogs Pseudopaludicola Miranda-Ribeiro, 1926 includes 23 species, which occur throughout South America. Herein we describe a new species of Pseudopaludicola from the central region of the state of Minas Gerais (southeastern Brazil). This new species is distinguished by the adult morphology, the advertisement call, and molecular data. It is diagnosed mainly by its small size, terminal phalanges knobbed (lack of any expansion of the digital tips), proportionally short hind limbs, and its advertisement call composed of series of two-pulsed notes, emitted at a high repetition rate. In addition, we report the occurrence of the new species in the southern foothills of the Serra do Cipó National Park, at elevations lower than 800 m above sea level (a.s.l). The sister species of this new taxon is P. mineira Lobo, 1994, which occurs in rupestrian grasslands above 1200 m a.s.l. at the Serra do Cipó National Park and in Serra do Cabral, both in the state of Minas Gerais, Brazil. We also redescribe the advertisement call of P. mineira based on recordings from topotypical males and compare it to calls of related species.
We investigate the characteristics of infrastructure as an asset class from an investment perspective of a limited partner. While non U.S. institutional investors gain exposure to infrastructure assets through a mix of direct investments and private fund vehicles, U.S. investors predominantly invest in infrastructure through private funds. We find that the stream of cash flows delivered by private infrastructure funds to institutional investors is very similar to that delivered by other types of private equity, as reflected by the frequency and amounts of net cash flows. U.S. public pension funds perform worse than other institutional investors in their infrastructure fund investments, although they are exposed to underlying deals with very similar project stage, concession terms, ownership structure, industry, and geographical location. By selecting funds that invest in projects with poor financial performance, U.S. public pension funds have created an implicit subsidy to infrastructure as an asset class, which we estimate within the range of $730 million to $3.16 billion per year depending on the benchmark.
Multiplex families with a high prevalence of a psychiatric disorder are often examined to identify rare genetic variants with large effect sizes. In the present study, we analysed whether the risk for bipolar disorder (BD) in BD multiplex families is influenced by common genetic variants. Furthermore, we investigated whether this risk is conferred mainly by BD-specific risk variants or by variants also associated with the susceptibility to schizophrenia or major depression. In total, 395 individuals from 33 Andalusian BD multiplex families as well as 438 subjects from an independent, sporadic BD case-control cohort were analysed. Polygenic risk scores (PRS) for BD, schizophrenia, and major depression were calculated and compared between the cohorts. Both the familial BD cases and unaffected family members had significantly higher PRS for all three psychiatric disorders than the independent controls, suggesting a high baseline risk for several psychiatric disorders in the families. Moreover, familial BD cases showed significantly higher BD PRS than unaffected family members and sporadic BD cases. A plausible hypothesis is that, in multiplex families with a general increase in risk for psychiatric disease, BD development is attributable to a high burden of common variants that confer a specific risk for BD. The present analyses, therefore, demonstrated that common genetic risk variants for psychiatric disorders are likely to contribute to the high incidence of affective psychiatric disorders in the multiplex families. The PRS explained only part of the observed phenotypic variance and rare variants might have also contributed to disease development.
The semantics of adjectives related to nominals denoting societal roles, such as presidential (from president), have remained understudied. We examine the semantics of what we call role-denoting relational adjectives, providing a formal analysis using the notion of a frame, a unified representation for lexical knowledge, world knowledge, and context. The frames we propose are based on a constructivist philosophical understanding of social roles, leading us to posit a multi-tiered ontology of events and individuals. Using frames and our ontology, we provide a general semantics for role-denoting relational adjectives and roles
In the context of limited donor pool in cardiothoracic transplantation, utilization of organs from high risk donors, such as suicidal hanging donors, while ensuring safety, is under consideration. We sought to evaluate the outcomes of lung transplantations (LTx) that use organs from this group.
Between January 2011 and December 2015, 265 LTx were performed at our center. Twenty-two recipients received lungs from donors after suicidal hanging (group 1). The remaining 243 transplantations were used as a control (group 2). Analysis of recipient and donor characteristics as well as outcomes was performed.
No statistically significant difference was found in the donor characteristics between analyzed groups, except for higher incidence of cardiac arrest, younger age and smoking history of hanging donors (P < .001, P = .022 and P = .0042, respectively). Recipient preoperative and perioperative characteristics were comparable. Postoperatively in group 1 there was a higher incidence of extracorporeal life support (27.3 vs 9.1%, P = .019). There were no significant differences in chronic lung allograft dysfunction-free survival between group 1 and 2: 92.3 vs 94% at 1 year and 65.9 vs 75.5% at 3 years (P = .99). The estimated cumulative survival rate was also similar between groups: 68.2 vs 83.2% at 1 year and 68.2% versus 72% at 3 years (P = .3758).
Hanging as a donor cause of death is not associated with poor mid-term survival or chronic lung allograft dysfunction following transplantation. These results encourage assessment of lungs from hanging donors, and their consideration for transplantation.
Discourses in the historical (or narrative) use of the simple present in English prohibit backshifting, though they allow forward sequencing. Unlike both reference time theories and discourse coherence theories of these temporal inferences, we propose that backshifting has a different source from narrative progression. In particular, we argue that backshifting arises through anaphora to a salient event in the preceding discourse.
Biologische Signalwege bilden komplexe Netzwerke aus, um die Zellantwort sensibel regulieren zu können. Systembiologische Ansätze werden eingesetzt, um biologische Systeme anhand von Computer-gestützten Modellen zu untersuchen. Ein mathematisches Modell erlaubt, neben der logischen Erfassung der Regulation des biologischen Systems, die systemweite Simulation des dynamischen Verhaltens und Analyse der Robustheit und Anfälligkeit.
Der TNFR1-vermittelte Signalweg reguliert essenzielle Zellvorgänge wie Entzündungsantworten,
Proliferation und Zelltod. TNFR1 wird von dem Zytokin TNF-α stimuliert und fördert daraufhin die Bildung verschiedener makromolekularer Komplexe, welche unterschiedliche Zellantworten einleiten, von der Aktivierung des Transkriptionsfaktors NF-κB, welcher die Expression von proliferationsfördernden Genen reguliert, bis zu zwei Formen des Zelltods, der Apoptose und der Nekroptose. Die Regulation der verschiedenen Zellantworten wird auch als molekularer Schalter bezeichnet. Die exakten molekularen Vorgänge, welche die Zellantwort modulieren, sind noch nicht vollständig entschlüsselt. Eine Fehlregulation des Signalwegs kann chronische Entzündungen hervorrufen oder die Entstehung von Tumoren fördern.
In dieser Thesis haben wir die neuesten Erkenntnisse der Forschung des TNFR1-Signalwegs anhand von umfangreichen Interaktionsdaten aus der Literatur erstmals in einem Petrinetz-Modell erfasst und analysiert. Das manuell kuratierte Modell umfasst die sequenziellen Prozesse der NF-κB-Aktivierung, Apoptose und Nekroptose und berücksichtigt den Einfluss posttranslationaler Modifikationen.
Weiterhin wurden Analysemethoden für Signalwegs-Modelle entwickelt, welche die spezifischen Anforderungen dieser biologischen Systeme berücksichtigen und eine biologisch motivierte Netzwerkanalyse ermöglichen. Die Manatee-Invarianten identifizieren Signalflüsse im Gleichgewichtszustand in Modellen, die Zyklen aufweisen, und werden als Linearkombination von Transitions-Invarianten gebildet. Diese Signalflüsse erfassen idealerweise einen Prozess von der Rezeptorstimulation zur Zellantwort in einem Modell eines Signalwegs. Die Bestimmung aller möglichen Signalflüsse in Modellen von Signalwegen ist eine notwendige Voraussetzung für weitere biologisch motivierte Analysen, wie die in silico-Knockout Analyse. Wir haben ebenfalls ein neues Konzept zur Untersuchung von in silico-Knockouts vorgestellt. Die Effekte der in silico-Knockouts auf einzelne Komplexe und Prozesse des Signalwegs werden in der in silico-Knockout-Matrix repräsentiert. Wir haben die Software-Anwendung isiKnock entwickelt, welche beide Konzepte kombiniert und eine systematische Knockout-Analyse von Petrinetz-Modellen unterstützt.
Das Petrinetz-Modell des TNFR1-Signalwegs wurde auf seine elementaren Eigenschaften geprüft und die etablierten Analysen wie Platz-Invarianten und Transitions-Invarianten durchgeführt. Hierbei konnten die Transitions-Invarianten nicht in allen Fällen komplette biologische Signalflüsse beschreiben. Wir haben ebenfalls die neu vorgestellten Methoden auf das Petrinetz-Modell angewandt. Anhand der Manatee-Invarianten konnten wir die zusammenhängenden Signalflüsse identifizieren und nach ihrem biologischen Ausgang klassifizieren sowie die Auswirkungen der Rückkopplungen untersuchen. Wir konnten zeigen, dass die survival-Antwort durch die Aktivierung von NF-κB am häufigsten auftritt, danach die Apoptose, gefolgt von der Nekroptose. Die alternativen Signalflüsse in Form der Manatee-Invarianten spiegeln die Robustheit des biologischen Systems wider. Wir führten eine ausgiebige in silico-Knockout-Analyse basierend auf den Manatee-Invarianten durch, um die Proteine des Signalwegs nach ihrem Einfluss einzustufen und zu gruppieren. Die Proteine des Komplex I wiesen hierbei den größten Einfluss auf, angeführt von der Rezeptorstimulation und RIP1. Wir betrachteten und diskutierten die Regulation des molekularen Schalters anhand der Knockout-Analyse von selektierten Proteinen und deren Auswirkung auf wichtige Komplexe im Modell. Wir identifizierten die Ubiquitinierung in Komplex I sowie die NF-κB-abhängige Genexpression als die wichtigen Kontrollpunkte des TNFR1-Signalwegs. In Komplex II ist die Regulation der Aktivierung der Caspase-Aktivität entscheidend.
Die umfangreiche Netzwerkanalyse basierend auf Manatee-Invarianten und systematischer in silico-Knockout-Analyse verifizierte das Petrinetz-Modell und erlaubte die Untersuchung der Robustheit und Anfälligkeit des Systems. Die neu entwickelten Methoden ermöglichen eine fundierte, biologisch relevante Untersuchung von in silico-Modellen von Signalwegen. Der systembiologische Ansatz unterstützt die Aufklärung der Regulation und Funktion des verflochtenen Netzwerks des TNFR1-Signalwegs.
Im Folgenden soll ein kurzer Überblick gegeben werden über die schiitische Sicht der frühislamischen Geschichte sowie über einige Phänomene, die sich daraus ergeben haben. Sie sind Hindernisse einer islamischen Einheit und müssten, sollte ein ernsthafter Versuch einer solchen verfolgt werden, mit deutlich mehr Mut angegangen werden. Dabei geht es hier weniger darum, alle Unterschiede zwischen Schia und Sunna aufzuzeigen, als sich auf die wirklich problematischen Felder zu konzentrieren, die nicht Folgen späterer, oft zufälliger Entwicklungen sind, sondern Weichenstellungen, die in der Frühgeschichte zu verorten sind. Bisher werden diese neuralgischen Punkte bei den Versuchen einer islamischen Ökumene, um diesen sehr christlich belegten Begriff an dieser Stelle doch einmal zu verwenden, meist umgangen, weil man um ihre Brisanz und Sprengkraft weiß. Doch müsste die Auseinandersetzung mit den unterschiedlichen Geschichtsbildern erfolgen, da sie ein wichtiges innerislamisches Differenzkriterium bilden; zumindest sollte man sich klar darüber sein, dass es unterschiedliche Geschichtsbilder gibt und sie ein Differenzkriterium bilden.
The research of phraseology in fiction has gained importance from its wide potential of its application in modern literature. This creative linguistic phenomenon manifests itself primarily in the branch of “author phraseologism”. Author phraseologism indicates the phraseological units that appear in the works of a certain author; these units may occur frequently or may occur in isolated cases throughout the his/her work. Author phraseologism is regarded as a main source of creative expressions. If these creative expressions are subjected to circulation and wide usage, they develop into established phraseologisms that become well-known to the public. A renowned exemplification of this is the quotation from Hamlet “to be or not to be, that is the question”. Generally, these author phraseologisms have certain functions to fulfil; they give the literary work a semantic and aesthetic value.
Therefore, this paper attempts to explore Peter's active creative work on his poetic language since he rarely tends to use the fairly frozen idiomatic phrases that have widely been used before his time. This research paper analyses these creative phrases syntactically, semantically and metaphorically by identifying the phraseological potential, aesthetic value and poetic function in some of Peter's short stories.
The selected short stories of Peters that are analysed, are a part of the most modern literary works. This could be the reason for that his newly created phrases, have not been acknowledged as fixed phrases yet. The fact that the phrases are not repeated within the same story or in other works by himself, may be one of the reasons for that the investigated examples cannot be considered as anchored phraseologisms.
What gives this paper importance is the study of the creative language of Peters. Furthermore, this paper contributes to synchronous and documentary research of phraseology in the German literature. Peter's works has been previously studied from a literary and cultural point of view, however the linguistic aspects of his works were not given sufficient attention.
In diesem Aufsatz wird der Entwicklungsprozess des digitalen Lehr- und Lernspiels 'Berlin 3D entdecken!', das in Kooperation von Bursaer und Jenaer DaF-DozentInnen entwickelt wurde, unter technischen und didaktischen Aspekten vorgestellt. Digitalspiel-basiertes Fremdsprachen Lernen (DGBLL) und Gamifizierung sind gegenwärtige Tendenzen im computerbasierten Fremdsprachenlernen. Die Millenium-Generationen, die sog. Digital Natives, lernen durch digitale (Lern-)Spiele diverser Art (Prensky 2001). Während die Jugendlichen digitale Sprachlernspiele als neues Material willkommen heißen, bleiben die Lehrpersonen aus verschiedenen Gründen eher skeptisch, was oft kritisiert wird (Allsop et al. 2013, Blume 2017, Chandler 2013, Emin-Martinez & Ney 2013, Gerber & Price 2013, Wagner & Mitgutsch 2009). Doch die Kritik an den Lehrenden ist nicht gerechtfertigt, da fast alle Spiele dieser Art als Medium zum individuellen Lernen in außerschulischen Kontexten konzipiert worden sind und sich daher nur bedingt in den Unterricht integrieren lassen. Es bleibt offen, wie Lehrende ein Selbstlernmedium im Unterricht verwenden können. Der entscheidende Grund zurückhaltender Einstellungen von Lehrenden ist, dass derzeit kein digitales Spiel vorhanden ist, das sie in ihren DaF-Klassen zu unterrichtlichen Zwecken einsetzen können, d.h. es gibt kein digitales Lehrspiel! Um zur Lösung dieses Problems beizutragen, wurde ein digitales DaF-Lehrspiel entwickelt: 'Berlin 3D entdecken!' Durch dieses Spiel können DaF-Lehrende in eigenen Klassen spielend lehren. Auf dem Sprachniveau B1+ liefert das Spiel landeskundliche Informationen über fünf Sehenswürdigkeiten in Berlin Mitte. Als RPG (Role Play Game) konzipiertes Spiel enthält es 3D-Modelle von historischen Bauten, die von Avataren realitätsnah erkundet werden. Durch 3D-Präsentationen, interaktive Übungen und einen Abschlusstest bietet das Spiel die Möglichkeit, es in den Unterricht zu integrieren. Es wurden vier Grundversionen des Spiels entwickelt: für PC, Smartboard, Web und Mobil (Android & IOS).
Bu araştırmada, 2016 yılında U. Ü. bilimsel araştırma projelerini destekleme birimi (BAP) desteğiyle başlatılan bir proje kapsamında yapılan yabancı dil öğretiminde dijital oyunlar ve oyunlaştırılmış uygulamalar geliştirme çalışmaları ele alınmıştır. Proje sürecinde yapılan alanyazın taraması ve öğretmenlerle yapılan anket çalışması sonucunda yabancı dil öğrenimi ve öğretimi süreçlerinde 3B dijital oyunların yeterince kullanılmadığı ve öğretmenlerin dijital oyun kullanma ve geliştirme konusunda yeterli kuramsal ve uygulamalı bilgiye sahip olmadıkları belirlenmiştir. Bu sonuç dikkate alınarak yapılan bu çalışmanın üçüncü bölümünde öğretmenlere ve materyal geliştiricilere yol göstermek amacıyla dijital oyun geliştirme süreci aşama aşama somut örneklerle ortaya konmuş, bu süreçte kullanılabilecek, materyal geliştirme araçları ayrıntılı olarak tanıtılmıştır. Söz konusu proje süreçlerinde elde edilen ve bu çalışmada ortaya konan bilgilerin yabancı dil öğretiminde dijital oyunların yaygınlaşmasına ve yabancı dil öğretmenlerinin kendi dersleri için dijital oyun materyallerini geliştirmelerine katkı sağlanması hedeflenmektedir.
Teknoloji alanında sergilenen gelişmeler her dönemde birçok alana olduğu gibi yabancı dil öğretimi alanına da etki etmiş ve bu alandaki ortam, materyal, araç-gereç, yöntem, teknik vb. daha birçok değişkeni biçimlendirmiştir. Yabancı dil öğretiminin tarihsel gelişim sürecinde çağın teknik gelişmelerine paralel olarak ders kitapları, tepegöz saydamları, dia filmler, analog (kasetlerde) ve dijital (CD vb.) ses materyalleri, analog ve dijital filmler, dijital sunu materyalleri, bilgisayar destekli etkileşimli öğrenim uygulamaları gibi geniş bir materyal yelpazesi oluşmuştur. İlk kişisel bilgisayarın üretildiği 1980 yılından itibaren eğlencelik dijital oyunlar da geliştirilmiştir. 36 yıllık bu süreçte eğitsel dijital oyunlar da geliştirilmiş ve yabancı dil öğrenim/öğretim materyalleri yelpazesine eğitsel dijital oyunlar da eklenmiştir. Günümüzde piyasada birçok eğitsel dijital oyun mevcuttur ve bunlar donanım, yazılım, yapı, içerik vb. gibi özelliklerine göre çeşitli gruplara/türlere ayrılmaktadır.
White matter microstructural changes and episodic memory disturbances in late-onset bipolar disorder
(2018)
Background: Bipolar disorder (BD) has been associated with distributed network disruption, but little is known on how different clinical subtypes, particularly those with an earlier and later onset of disease, are related to connectivity changes in white matter (WM) tracts.
Methods: Diffusion tensor imaging (DTI) and volumetric measures were carried out in early-onset bipolar patients [(EOD) (n = 16)], late-onset bipolar disorder [(LOD)(n = 14)] and healthy controls (n = 32). We also computed ROI analysis of gray matter (GM) and white matter (WM) volumes using the regions with significant group differences in the DTI parameters. Cognitive and behavior measurements were analyzed between groups.
Results: Lower fraction of anisotropy (FA) in the right hemisphere comprising anterior thalamic radiation, fornix, posterior cingulate, internal capsule, splenium of corpus callosum was observed in the LOD in comparison with EOD; additionally, lower FA was also found in the LOD in comparison with healthy controls, mostly in the right hemisphere and comprising fibers of the splenium of the corpus callosum, cingulum, superior frontal gyrus and posterior thalamic radiation; LOD also showed worse episodic memory performance than EOD; no statistical significant differences between mood symptoms, WM and GM volumes were found between BD groups.
Conclusion: Even after correcting for age differences, LOD was associated with more extensive WM microstructural changes and worse episodic memory performance than EOD; these findings suggest that changes in the WM fiber integrity may be associated with a later presentation of BD, possibly due to mechanisms other than neuroprogression. However, these findings deserve replication in larger, prospective, studies.
Adorno pensou a filosofia moral em diversos momentos de sua carreira filosófica, notadamente em Minima Moralia (1951), Dialética Negativa (1966) e em seu curso publicado postumamente Probleme der Moralphilosophie (1996). Uma avaliação conjunta desses textos permite indicar a centralidade do que Adorno chamou de “dialética da moral” – entre impulso somático e racionalidade – na constituição da experiência do prático. Além disso, as reflexões sobre a moral são um momento privilegiado das análises metafilosóficas de Adorno, que identificam em boa parte da tradição filosófica ocidental sobre a moral a presença da dominação da natureza interna – processo que caberia à dialética materialista da moral criticar e ajudar a transformar.
Brückenbauer in den Markt : wie Erfindungen an der Goethe-Uni ihren Weg in die Wirtschaft finden
(2018)
Background: Methotrexate (MTX) remains the anchor drug in rheumatoid arthritis (RA) treatment, but is poorly tolerated or contraindicated in some patients. There is a wealth of data supporting the use of abatacept in combination with MTX, but data on alternative conventional synthetic disease-modifying antirheumatic drug (csDMARD) combinations with abatacept are scarce.
Methods: In this post-hoc exploratory analysis, efficacy and safety data were extracted from abatacept RA studies in which combination with csDMARDs other than MTX was permitted: three interventional trials (ATTAIN, ASSURE, and ARRIVE) and one real-world study (ACTION). Patients with moderate-to-severe RA received abatacept in combination with MTX, hydroxychloroquine, sulfasalazine, azathioprine, or leflunomide for 6 months to 2 years according to the study design. Change from baseline in physical function (Health Assessment Questionnaire—Disability Index (HAQ-DI); all studies) and 28-joint Disease Activity Score (C-reactive protein) (DAS28 (CRP); ATTAIN, ARRIVE, and ACTION), American College of Rheumatology response rates (ATTAIN), and safety were assessed for individual and pooled csDMARD combinations for each trial. A meta-analysis was also performed on pooled data for HAQ-DI and DAS28 (CRP) across interventional trials.
Results: Across all four studies, 731 patients received abatacept plus one non-MTX csDMARD (hydroxychloroquine n = 152; sulfasalazine n = 123; azathioprine n = 59; and leflunomide n = 397) and 2382 patients received abatacept plus MTX. Mean changes from baseline in HAQ-DI scores for abatacept plus MTX (all csDMARDs pooled) vs abatacept plus a non-MTX csDMARD were –0.54 vs –0.44 (ATTAIN), –0.43 vs –0.43 (ASSURE), and –0.39 vs –0.36 (ARRIVE). Mean changes from baseline in DAS28 (CRP) and ACR response rates were also similar with abatacept plus MTX or non-MTX csDMARDs. Data for individual non-MTX csDMARDs (pooled across studies) and real-world data were consistent with these findings. Rates of treatment-related adverse events and serious adverse events, respectively, for abatacept plus one non-MTX csDMARD vs abatacept plus MTX were 35.7% vs 41.7% and 2.4% vs 2.3% (ATTAIN), 58.0% vs 55.9% and 4.2% vs 1.7% (ASSURE), and 38.1% vs 44.3% and 0.6% vs 2.9% (ARRIVE).
Conclusions: Abatacept in combination with non-MTX csDMARDs is clinically effective and well tolerated in patients with moderate-to-severe RA, providing similar benefits to those seen with abatacept plus MTX.
In dieser Arbeit soll identifiziert werden, welcher der zahlreichen Vertreter einer Arzneistoffklasse sich letztlich auf dem Markt durchsetzen kann und ob bestimmte pharmakokinetische, pharmakodynamische, klinische oder praktische Substanzeigenschaften retrospektiv für den Markterfolg einer Substanz verantwortlich gemacht werden können. Zudem stellt sich die Frage, ob und in wie fern Analogpräparate einen Nutzen in der Arzneimitteltherapie mit sich bringen, obwohl ihnen zum Zeitpunkt ihrer Markteinführung nur ein geringer Innovationsgrad zugebilligt wurde. Um derartige Rückschlüsse ziehen zu können wurden exemplarisch folgende fünf Arzneistoffklassen untersucht, die sich durch eine Vielzahl an Vertretern auszeichnen: Arsphenamine, Sulfonamide, Benzodiazepine, Glucocorticoide sowie Betablocker. Der Untersuchungszeitraum bemisst sich folglich vom Anfang des 20. Jahrhunderts, als industriell gefertigte, chemisch definierte hochpotente Wirkstoffe die Therapie zu bestimmen begannen, bis etwa zum letzten Drittel des 20. Jahrhunderts als Preise und Kostenerstattungsfragen zusätzlich zu Substanzeigenschaften für den Markterfolg mitbestimmend wurden.
Eastern boundary upwelling provides the conditions for high marine productivity in the Canary Current System off NW-Africa. Despite its considerable importance to fisheries, knowledge on this marine ecosystem is only limited. Here, parasites were used as indicators to gain insight into the host ecology and food web of two pelagic fish species, the commercially important species Trichiurus lepturus Linnaeus, 1758, and Nealotus tripes Johnson, 1865. Fish specimens of T. lepturus (n = 104) and N. tripes (n = 91), sampled from the Canary Current System off the Senegalese coast and Cape Verde Islands, were examined, collecting data on their biometrics, diet and parasitisation. In this study, the first parasitological data on N. tripes are presented. T. lepturus mainly preyed on small pelagic Crustacea and the diet of N. tripes was dominated by small mesopelagic Teleostei. Both host species were infested by mostly generalist parasites. The parasite fauna of T. lepturus consisted of at least nine different species belonging to six taxonomic groups, with a less diverse fauna of ectoparasites and cestodes in comparison to studies in other coastal ecosystems (Brazil Current and Kuriosho Current). The zoonotic nematode Anisakis pegreffii occurred in 23% of the samples and could pose a risk regarding food safety. The parasite fauna of N. tripes was composed of at least thirteen species from seven different taxonomic groups. Its most common parasites were digenean ovigerous metacercariae, larval cestodes and a monogenean species (Diclidophoridae). The observed patterns of parasitisation in both host species indicate their trophic relationships and are typical for mesopredators from the subtropical epi- and mesopelagic. The parasite fauna, containing few dominant species with a high abundance, represents the typical species composition of an eastern boundary upwelling ecosystem.
Isolated complex I deficiency is a common biochemical phenotype observed in pediatric mitochondrial disease and often arises as a consequence of pathogenic variants affecting one of the ∼65 genes encoding the complex I structural subunits or assembly factors. Such genetic heterogeneity means that application of next-generation sequencing technologies to undiagnosed cohorts has been a catalyst for genetic diagnosis and gene-disease associations. We describe the clinical and molecular genetic investigations of four unrelated children who presented with neuroradiological findings and/or elevated lactate levels, highly suggestive of an underlying mitochondrial diagnosis. Next-generation sequencing identified bi-allelic variants in NDUFA6, encoding a 15 kDa LYR-motif-containing complex I subunit that forms part of the Q-module. Functional investigations using subjects’ fibroblast cell lines demonstrated complex I assembly defects, which were characterized in detail by mass-spectrometry-based complexome profiling. This confirmed a marked reduction in incorporated NDUFA6 and a concomitant reduction in other Q-module subunits, including NDUFAB1, NDUFA7, and NDUFA12. Lentiviral transduction of subjects’ fibroblasts showed normalization of complex I. These data also support supercomplex formation, whereby the ∼830 kDa complex I intermediate (consisting of the P- and Q-modules) is in complex with assembled complex III and IV holoenzymes despite lacking the N-module. Interestingly, RNA-sequencing data provided evidence that the consensus RefSeq accession number does not correspond to the predominant transcript in clinically relevant tissues, prompting revision of the NDUFA6 RefSeq transcript and highlighting not only the importance of thorough variant interpretation but also the assessment of appropriate transcripts for analysis.
The successful elimination of bacteria such as Streptococcus pneumoniae from a host involves the coordination between different parts of the immune system. Previous studies have explored the effects of the initial pneumococcal load (bacterial dose) on different representations of innate immunity, finding that pathogenic outcomes can vary with the size of the bacterial dose. However, others yield support to the notion of dose-independent factors contributing to bacterial clearance. In this paper, we seek to provide a deeper understanding of the immune responses associated to the pneumococcus. To this end, we formulate a model that realizes an abstraction of the innate-regulatory immune host response. Stability and bifurcation analyses of the model reveal the following trichotomy of pneumococcal outcomes determined by the bifurcation parameters: (i) dose-independent clearance; (ii) dose-independent persistence; and (iii) dose-limited clearance. Bistability, where the bacteria-free equilibrium co-stabilizes with the most substantial steady-state bacterial load is the specific result behind dose-limited clearance. The trichotomy of pneumococcal outcomes here described integrates all previously observed bacterial fates into a unified framework.
A point mutation in the Ncr1 signal peptide impairs the development of innate lymphoid cell subsets
(2018)
NKp46 (CD335) is a surface receptor shared by both human and mouse natural killer (NK) cells and innate lymphoid cells (ILCs) that transduces activating signals necessary to eliminate virus-infected cells and tumors. Here, we describe a spontaneous point mutation of cysteine to arginine (C14R) in the signal peptide of the NKp46 protein in congenic Ly5.1 mice and the newly generated NCRB6C14R strain. Ly5.1C14R NK cells expressed similar levels of Ncr1 mRNA as C57BL/6, but showed impaired surface NKp46 and reduced ability to control melanoma tumors in vivo. Expression of the mutant NKp46C14R in 293T cells showed that NKp46 protein trafficking to the cell surface was compromised. Although Ly5.1C14R mice had normal number of NK cells, they showed an increased number of early maturation stage NK cells. CD49a+ILC1s were also increased but these cells lacked the expression of TRAIL. ILC3s that expressed NKp46 were not detectable and were not apparent when examined by T-bet expression. Thus, the C14R mutation reveals that NKp46 is important for NK cell and ILC differentiation, maturation and function.
Weg mit den Talaren! Hoch die Doktorhüte! : vom Wandel der Zeremonialität an deutschen Universitäten
(2018)
"Unter den Talaren – Muff von 1000 Jahren": Dieser Slogan steht wie kaum ein anderer für die Aufbruchstimmung der 68er-Generation. Damit zielten die Hamburger Studenten auf das Verschweigen der NS-Vergangenheit ab, anschließend ging es aber auch den Talaren selbst an den Kragen. Seit einigen Jahren wird im zeremoniellen Raum der Universitäten vielfach experimentiert: Die Fächer bilden eine jeweils eigene Feierkultur aus – auf der Suche nach einem Übergang von der Universität in das berufliche Leben.
Die philosophische Erkenntnis in der 'Klage der Ceres' : Schillers Adaption des Proserpina-Mythos
(2018)
While Ceres behaves actively and energetically in the traditional myth, Friedrich von Schiller's poem 'Klage der Ceres' (1797) shows her within the same ancient plot but as a more emotional figure. This detailed analysis explains the poem's structure and the stylistic devices which lead to its philosophical impact. It also addresses the awareness that death is a part of life and discusses how art can help to reinvent traditional ideas.
We discuss the current developments by the European Twisted Mass Collaboration in extracting parton distribution functions from the quasi-PDF approach. We concentrate on the non-perturbative renormalization prescription recently developed by us, using the RI′ scheme. We show results for the renormalization functions of matrix elements needed for the computation of quasi-PDFs, including the conversion to the MS scheme, and for renormalized matrix elements. We discuss the systematic effects present in the Z-factors and the possible ways of addressing them in the future.
We show the first results for parton distribution functions within the proton at the physical pion mass, employing the method of quasi-distributions. In particular, we present the matrix elements for the iso-vector combination of the unpolarized, helicity and transversity quasi-distributions, obtained with Nf = 2 twisted mass cloverimproved fermions and a proton boosted with momentum = 0.83 GeV. The momentum smearing technique has been applied to improve the overlap with the proton boosted state. Moreover, we present the renormalized helicity matrix elements in the RI’ scheme, following the non-perturbative renormalization prescription recently developed by our group.