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Despite the recent availability of vaccines against severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2), there is an urgent need for specific anti-SARS-CoV-2 drugs. Monoclonal neutralizing antibodies are an important drug class in the global fight against the SARS-CoV-2 pandemic due to their ability to convey immediate protection and their potential to be used as both prophylactic and therapeutic drugs. Clinically used neutralizing antibodies against respiratory viruses are currently injected intravenously, which can lead to suboptimal pulmonary bioavailability and thus to a lower effectiveness. Here we describe DZIF-10c, a fully human monoclonal neutralizing antibody that binds the receptor-binding domain of the SARS-CoV-2 spike protein. DZIF-10c displays an exceptionally high neutralizing potency against SARS-CoV-2, retains full activity against the variant of concern (VOC) B.1.1.7 and still neutralizes the VOC B.1.351, although with reduced potency. Importantly, not only systemic but also intranasal application of DZIF-10c abolished the presence of infectious particles in the lungs of SARS-CoV-2 infected mice and mitigated lung pathology when administered prophylactically. Along with a favorable pharmacokinetic profile, these results highlight DZIF-10c as a novel human SARS-CoV-2 neutralizing antibody with high in vitro and in vivo antiviral potency. The successful intranasal application of DZIF-10c paves the way for clinical trials investigating topical delivery of anti-SARS-CoV-2 antibodies.
We present the data of the 2nd research expedition of the European Dry Grassland Group (EDGG), which was conducted in 2010 in Central Podolia, Ukraine. The aim was to collect plot data to compare Ukrainian dry grasslands with those of other parts of Europe in terms of syntaxonomy and biodiversity. We sampled 21 nested-plot series (0.0001–100 m2) and 184 normal plots (10 m2) covering the full variety of dry grassland types occurring in the study region. For all plots, we recorded species composi-tion of terrestrial vascular plants, bryophytes and lichens, while for the 226 10-m2 plots we estimated and measured percentage cover of all species, structural, topographic, soil and landuse parameters. The 10-m² plots were used for phytosociological classification based on iteratively refined TWINSPAN classification as well as for DCA ordination. Differences between the derived vegetation types with respect to environmental conditions and species richness were assessed with ANOVAs. We assigned our plots to nine association-level units but refrained from placing them into formal associations with two exceptions. In the study area, dry grasslands of the Festuco-Brometea were far more common than those of the Koelerio-Corynephoretea. Among the Festuco-Brometea, xeric Festucetalia valesiacae grasslands were more frequent and represented by the Festucion valesiacae (2 associations, including the Allio taurici-Dichanthietum ischaemi ass. nova) and the Stipion lessingianae (1) compared to the Brachypodietalia pinnati with the Agrostio vinealis-Avenulion schellianae (3). The Koelerio-Corynephoretea were represented by three associations, each from a different order and alliance: basiphilous outcrops (Alysso alyssoidis-Sedetalia: Alysso alyssoidis-Sedion?), acidophilous outcrops (Sedo-Scleranthetalia: Veronico dillenii-Sedion albi?) and mesoxeric sandy grasslands (Trifolio arvensis-Festucetalia ovinae: Agrostion vinealis). We discuss the issue of the mesoxeric order Galietalia veri placed within the Molinio-Arrhenatheretea by Ukrainian authors and conclude that the content of that order would probably be better placed in the mesoxeric orders of the Koelerio-Corynephoretea and Festuco-Brometea. Other syntaxonomic questions could not be solved with our geographically limited dataset and await a supraregional analysis, e.g. whether the Ukrainian outcrop communities should be assigned to the same alliances as known from Central Europe or rather represent new vicariant units. The analysis of the biodiversity patterns showed that at a grain size of 10 m2, Podolian Koelerio-Corynephoretea communities were overall richer than Festuco-Brometea communities (46.4 vs. 40.6 species). This difference was due to the Koelerio-Corynephoretea containing twice as many bryophytes and nine times more lichens, while vascular plant species richness did not differ significantly between classes. The orders within the classes showed no real differences in species richness. The richness patterns observed in Podolia were almost the opposite of those usually found in dry grasslands, where Brachypodietalia pinnati are richer than Festucetalia valesiacae, and these richer than stands of the Koelerio-Corynpehoretea – and we do not have a good explanation for these idiosyncrasies. In conclusion, Podolian dry grasslands behave quite unexpectedly regarding biodiversity, and their syntaxonomy is still poorly understood. These knowledge gaps can only be addressed with supranational analyses based on comprehensive datasets.
This report provides a brief review of the 20th annual meeting of the German Language Branch of the Society of Environmental Toxicology and Chemistry (SETAC GLB) held from September 7th to 10th 2015 at ETH (Swiss Technical University) in Zurich, Switzerland. The event was chaired by Inge Werner, Director of the Swiss Centre for Applied Ecotoxicology (Ecotox Centre) Eawag-EPFL, and organized by a team from Ecotox Centre, Eawag, Federal Office of the Environment, Federal Office of Agriculture, and Mesocosm GmbH (Germany). Over 200 delegates from academia, public agencies and private industry of Germany, Switzerland and Austria attended and discussed the current state of science and its application presented in 75 talks and 83 posters. In addition, three invited keynote speakers provided new insights into scientific knowledge ‘brokering’, and—as it was the International Year of Soil—the important role of healthy soil ecosystems. Awards were presented to young scientists for best oral and poster presentations, and for best 2014 master and doctoral theses. Program and abstracts of the meeting (mostly in German) are provided as Additional file 1.
The inclusive charged particle transverse momentum distribution is measured in proton–proton collisions at s=900 GeV at the LHC using the ALICE detector. The measurement is performed in the central pseudorapidity region (|η|<0.8) over the transverse momentum range 0.15<pT<10 GeV/c. The correlation between transverse momentum and particle multiplicity is also studied. Results are presented for inelastic (INEL) and non-single-diffractive (NSD) events. The average transverse momentum for |η|<0.8 is 〈pT〉INEL=0.483±0.001 (stat.)±0.007 (syst.) GeV/c and 〈pT〉NSD=0.489±0.001 (stat.)±0.007 (syst.) GeV/c, respectively. The data exhibit a slightly larger 〈pT〉 than measurements in wider pseudorapidity intervals. The results are compared to simulations with the Monte Carlo event generators PYTHIA and PHOJET.
Background: Alzheimer's disease is a common debilitating dementia with known heritability, for which 20 late onset susceptibility loci have been identified, but more remain to be discovered. This study sought to identify new susceptibility genes, using an alternative gene-wide analytical approach which tests for patterns of association within genes, in the powerful genome-wide association dataset of the International Genomics of Alzheimer's Project Consortium, comprising over 7 m genotypes from 25,580 Alzheimer's cases and 48,466 controls.
Principal findings: In addition to earlier reported genes, we detected genome-wide significant loci on chromosomes 8 (TP53INP1, p = 1.4×10−6) and 14 (IGHV1-67 p = 7.9×10−8) which indexed novel susceptibility loci.
Significance: The additional genes identified in this study, have an array of functions previously implicated in Alzheimer's disease, including aspects of energy metabolism, protein degradation and the immune system and add further weight to these pathways as potential therapeutic targets in Alzheimer's disease.
Background: 15-20% of all patients initially diagnosed with colorectal cancer develop metastatic disease and surgical resection remains the only potentially curative treatment available. Current 5-year survival following R0-resection of liver metastases is 28-39%, but recurrence eventually occurs in up to 70%. To date, adjuvant chemotherapy has not improved clinical outcomes significantly. The primary objective of the ongoing LICC trial (L-BLP25 In Colorectal Cancer) is to determine whether L-BLP25, an active cancer immunotherapy, extends recurrence-free survival (RFS) time over placebo in colorectal cancer patients following R0/R1 resection of hepatic metastases. L-BLP25 targets MUC1 glycoprotein, which is highly expressed in hepatic metastases from colorectal cancer. In a phase IIB trial, L-BLP25 has shown acceptable tolerability and a trend towards longer survival in patients with stage IIIB locoregional NSCLC.
Methods: This is a multinational, phase II, multicenter, randomized, double-blind, placebo-controlled trial with a sample size of 159 patients from 20 centers in 3 countries. Patients with stage IV colorectal adenocarcinoma limited to liver metastases are included. Following curative-intent complete resection of the primary tumor and of all synchronous/metachronous metastases, eligible patients are randomized 2:1 to receive either L-BLP25 or placebo. Those allocated to L-BLP25 receive a single dose of 300 mg/m2 cyclophosphamide (CP) 3 days before first L-BLP25 dose, then primary treatment with s.c. L-BLP25 930 mug once weekly for 8 weeks, followed by s.c. L-BLP25 930 mug maintenance doses at 6-week (years 1&2) and 12-week (year 3) intervals unless recurrence occurs. In the control arm, CP is replaced by saline solution and L-BLP25 by placebo. Primary endpoint is the comparison of recurrence-free survival (RFS) time between groups. Secondary endpoints are overall survival (OS) time, safety, tolerability, RFS/OS in MUC-1 positive cancers. Exploratory immune response analyses are planned. The primary endpoint will be assessed in Q3 2016. Follow-up will end Q3 2017. Interim analyses are not planned.
Discussion: The design and implementation of such a vaccination study in colorectal cancer is feasible. The study will provide recurrence-free and overall survival rates of groups in an unbiased fashion. Trial Registration EudraCT Number 2011-000218-20
Electroencephalography (EEG) represents a widely established method for assessing altered and typically developing brain function. However, systematic studies on EEG data quality, its correlates, and consequences are scarce. To address this research gap, the current study focused on the percentage of artifact-free segments after standard EEG pre-processing as a data quality index. We analyzed participant-related and methodological influences, and validity by replicating landmark EEG effects. Further, effects of data quality on spectral power analyses beyond participant-related characteristics were explored. EEG data from a multicenter ADHD-cohort (age range 6 to 45 years), and a non-ADHD school-age control group were analyzed (ntotal = 305). Resting-state data during eyes open, and eyes closed conditions, and task-related data during a cued Continuous Performance Task (CPT) were collected. After pre-processing, general linear models, and stepwise regression models were fitted to the data. We found that EEG data quality was strongly related to demographic characteristics, but not to methodological factors. We were able to replicate maturational, task, and ADHD effects reported in the EEG literature, establishing a link with EEG-landmark effects. Furthermore, we showed that poor data quality significantly increases spectral power beyond effects of maturation and symptom severity. Taken together, the current results indicate that with a careful design and systematic quality control, informative large-scale multicenter trials characterizing neurophysiological mechanisms in neurodevelopmental disorders across the lifespan are feasible. Nevertheless, results are restricted to the limitations reported. Future work will clarify predictive value.
Background: Simultaneous pancreas kidney transplantation (SPK), pancreas transplantation alone (PTA) or pancreas transplantation after kidney (PAK) are the only curative treatment options for patients with type 1 (juvenile) diabetes mellitus with or without impaired renal function. Unfortunately, transplant waiting lists for this indication are increasing because the current organ acceptability criteria are restrictive; morbidity and mortality significantly increase with time on the waitlist. Currently, only pancreas organs from donors younger than 50 years of age and with a body mass index (BMI) less than 30 are allocated for transplantation in the Eurotransplant (ET) area. To address this issue we designed a study to increase the available donor pool for these patients.
Methods/Design: This study is a prospective, multicenter (20 German centers), single blinded, non-randomized, two armed trial comparing outcome after SPK, PTA or PAK between organs with the currently allowed donor criteria versus selected organs from donors with extended criteria. Extended donor criteria are defined as organs procured from donors with a BMI of 30 to 34 or a donor age between 50 and 60 years. Immunosuppression is generally standardized using induction therapy with Myfortic, tacrolimus and low dose steroids. In principle, all patients on the waitlist for primary SPK, PTA or PAK are eligible for the clinical trial when they consent to possibly receiving an extended donor criteria organ. Patients receiving an organ meeting the current standard criteria for pancreas allocation (control arm) are compared to those receiving extended criteria organ (study arm); patients are blinded for a follow-up period of one year. The combined primary endpoint is survival of the pancreas allograft and pancreas allograft function after three months, as an early relevant outcome parameter for pancreas transplantation.
Discussion: The EXPAND Study has been initiated to investigate the hypothesis that locally allocated extended criteria organs can be transplanted with similar results compared to the currently allowed standard ET organ allocation. If our study shows a favorable comparison to standard organ allocation criteria, the morbidity and mortality for patients waiting for transplantation could be reduced in the future.
Trial registered at: NCT01384006
Rezensionen [2017]
(2017)
156 Ansari, Christine (Hrsg.): Adoleszenz in Medienkontexten. Literaturrezeption, Medienwirkung und Jugendmedienschutz (judith mathez)
158 Bachmann, Christian A. / Emans, Laura / Schmitz-Emans, Monika (Hrsg.): Bewegungsbücher. Spielformen, Poetiken, Konstellationen (gundel mattenklott)
160 Ballis, Anja /Schlachter, Birgit (Hrsg.): Schätze der Kinder- und Jugendliteratur wiederentdeckt. Frühe Lektüreerfahrung und Kanonbildung im akademischen Kontext (ernst seibert)
162 Benner, Julia: Federkrieg. Kinder- und Jugendliteratur gegen den Nationalsozialismus 1933 – 1945 (linde storm)
164 Born, Stefan: Allgemeinliterarische Adoleszenzromane. Untersuchungen zu Herrndorf, Regener, Strunk, Kehlmann und anderen (lena hoffmann)
166 Börnchen, Stefan: Poetik der Linie. Wilhelm Busch, Max und Moritz und die Tradition (lukas sarvari)
168 Burwitz-Melzer, Eva /O’Sullivan, Emer (Hrsg.): Einfachheit in der Kinder- und Jugendliteratur. Ein Gewinn für den Fremdsprachenunterricht (roland alexander issler)
169 Emde, Oliver /Möller, Lukas /Wicke, Andreas (Hrsg.): Von »Bibi Blocksberg« bis »TKKG«. Kinderhörspiele aus gesellschafts- und kulturwissenschaftlicher Perspektive (anika ullmann)
171 Ferstl, Paul /Walach, Thomas / Zahlmann, Stefan (Hrsg.): Fantasy Studies (maren bonacker)
173 Giesa, Felix: Graphisches Erzählen von Adoleszenz. Deutschsprachige Autorencomics nach 2000 (michael staiger)
175 Hahn, Heidi / Laudenberg, Beate / Rösch, Heidi (Hrsg.): »Wörter raus!?« Zur Debatte um eine diskriminierungsfreie Sprache im Kinderbuch (julia benner)
177 Haug, Christine / Frimmel, Johannes (Hrsg.): Schulbücher um 1800. Ein Spezialmarkt zwischen staatlichem, volksaufklärerischem und konfessionellem Auftrag (ortwin beisbart)
179 Hollerweger, Elisabeth /Stemmann, Anna (Hrsg.): Narrative Delikatessen. Kulturelle Dimensionen von Ernährung (sonja loidl)
180 Hopp, Margarete: Sterben, Tod und Trauer im Bilderbuch seit 1945 (iris schäfer)
182 Huemer, Georg: Mira Lobe. Doyenne der österreichischen Kinder- und Jugendliteratur (andreas schumann)
183 Josting, Petra (Hrsg.): Andreas Steinhöfel, Bielefelder Poet in Residence 2014 (heinke kilian)
185 Josting, Petra /Roeder, Caroline /Dettmar, Ute (Hrsg.): Immer Trouble mit Gender. Genderperspektiven in Kinder- und Jugendliteraturforschung und -medien (jana mikota)
187 Kurwinkel, Tobias /Schmerheim, Philipp /Sevi, Annika (Hrsg.): Michael Ende intermedial. Von Lokomotivführern, Glücksdrachen und dem (phantastischen) Spiel mit Mediengrenzen (michael stierstorfer)
188 Mikota, Jana / Pecher, Claudia Maria / von Glasenapp, Gabriele (Hrsg.): Literarisch-kulturelle Begegnungen mit dem Judentum. Beiträge zur kinderliterarischen Fachöffentlichkeit (susanne blumesberger)
190 Müller, Karla / Decker, Jan-Oliver / Krah, Hans / Schilcher, Anita (Hrsg.): Genderkompetenz mit Kinder- und Jugendliteratur entwickeln: Grundlagen – Analysen – Modelle (annette kliewer)
192 Nikolajeva, Maria: Reading for Learning. Cognitive Approaches to Children’s Literature (sabine fuchs)
194 Paul, Lissa / Johnston, Rosemary R. / Short, Emma (Hrsg.):Children’s Literature and Culture of the First World War.(julia benner)
195 Payrhuber, Franz-Josef / Meier, Bernhard(Hrsg.): Franz, Kurt: Kinderlyrik. Geschichte, Formen, Rezeption(ludger scherer)
197 Payrhuber, Franz-Josef:Gedichte entdecken. Wege zu Gedichten in der ersten bis sechsten Klasse (andreas schumann)
198 Pohlmann, Carola (Hrsg): Kinder- und Jugendliteratur. Sammeln und Erwerben (wolfgang wangerin)
200 Pompe, Anja (Hrsg): Kind und Gedicht. Wie wir lesen lernen (heinz-jürgen kliewer)
202 Preindl, Nadia:Russische Kinderliteratur im europäischen Exil der Zwischenkriegszeit (verena rutschmann)
204 Richter, Karin: Die Kinder- und Jugend-literatur der DDR. Entwicklungslinien – Themen und Genres. Autorenporträts und Textanalysen (maria becker)
206 Riemhofer, Andra:Interkulturelle Kinder- und Jugendliteratur in Deutschland. Lesen auf eigene Gefahr (roger meyer)
208Roeder, Caroline (Hrsg.): Himmel und Hölle. Raumerkundungen – interdisziplinär & in schulischer Praxis (claudia blei-hoch)
210 Ruzicka Kenfel, Vejka (Hrsg.): New Trends in Children’s Literature Research. Twenty-first Century Approaches (2000–2012) from the University of Vigo (Spain) (susanne blumesberger)
212 Schäfer, Iris:Von der Hysterie zur Magersucht. Adoleszenz und Krankheit in Romanen und Erzählungen der Jahrhundert- und der Jahrtausendwende (philipp schmerheim)
214 Scherer, Gabriela / Volz, Steffen (Hrsg.): Im Bildungsfokus: Bilderbuchrezeptions-forschung (margarete hopp)
216 Schmitt, Susann Sophie:Nachwuchs für die Literatur. Kinder- und Jugendprogramme ausgewählter Literaturhäuser Deutschlands, Österreichs und der Schweiz (renate grubert)
217 Seelinger Trites, Roberta:Literary Conceptu-alizations of Growth. Metaphors and Cogni-tion in Adolescent Literature (iris schäfer)
219 Seifert, Martina:Die Bilderfalle. Kanada in der deutschsprachigen Kinder- und Jugend-literatur: Produktion und Rezeption (sabine planka)
222 Stein, Daniel / Thon, Jan-Noël (Hrsg.): From Comic Strips to Graphic Novels. Contributions to the Theory and History of Graphic Narrative (anna stemmann)
223 Tomberg, Markus (Hrsg.): Alle wichtigen Bücher handeln von Gott. Religiöse Spuren in aktueller Kinder- und Jugendliteratur (martin anker)
The Compressed Baryonic Matter (CBM) experiment is a dedicated heavy ion collision experiment at the FAIR facility. It will be one of the first HEP experiments which works in a triggerless mode: data received in the DAQ from the detectors will not be associated with events by a hardware trigger anymore. All raw data within a giventime period will be collected continuously in containers, so-called time-slices. The task of the reconstruction algorithms is to create events out of this raw data stream. In this contribution, the optimization of the reconstruction software in the RICH detector to the free-streaming data flow is presented. The implementation of ring reconstruction algorithms which use time measurements of the hits as an additional parameter is discussed.
In unserem Beitrag gehen wir der Frage nach, wie Erwachsene neue Fähigkeiten und Fertigkeiten zum mündlichen Kommunizieren erwerben, d.h. aneignen. Ziel ist es, die beteiligten Prozesse für Analyse-, Beratungs- und Vermittlungszwecke zu systematisieren, um Antworten auf die folgenden Fragen zu finden: Welche Teilfähigkeiten werden zum mündlichen Kommunizieren überhaupt benötigt? Welche lassen sich leicht – welche nur schwer oder vielleicht gar nicht vermitteln bzw. aneignen? Welche Methoden eignen sich für die Vermittlung welcher Fähigkeiten? Ausgangspunkt unserer Überlegungen sind praktische Fragen des Kompetenzerwerbs, d.h. des Erwerbs der Fähigkeit, angemessen mündlich kommunizieren zu können. Wir gehen davon aus, dass es sich hierbei um eine spezifische Kompetenz handelt, die sich von anderen Kompetenzen unterscheidet (vgl. Fiehler/ Schmitt i.d.Bd.). Ihre Besonderheit liegt in den spezifischen Bedingungen der mündlichen Kommunikation begründet: Gespräche und Diskurse sind immer das Resultat aller daran Beteiligter, so dass die Anteile und beteiligten Kompetenzen des Einzelnen weniger offensichtlich sind als bei individuellen Tätigkeiten. Mündliche Kommunikation ist durch ihre Flüchtigkeit, Prozesshaftigkeit, Interaktivität und Musterhaftigkeit gekennzeichnet (vgl. Deppermann i.d.Bd., Abschn. 3). Die Bewältigung mündlicher Kommunikation erfordert ein spezifisches Ensemble von Wissen und Fertigkeiten, die sich zusammenfassend als Gesprächskompetenz beschreiben lassen. Auch wenn wir uns in diesem Beitrag auf die Gesprächskompetenz konzentrieren, sind wir nicht der Auffassung, dass der faktische Gesprächsverlauf ausschließlich eine Funktion dieser Kompetenz ist. Vielmehr spielen andere Faktoren wie Emotionen und Affekte, Beziehungs- und Rollenfragen ebenfalls eine Rolle.
In dem folgenden Beitrag beschäftigen wir uns mit den Merkmalen und Besonderheiten diskursanalytischer Fortbildungskonzepte. Unter diskursanalytischen Konzepten verstehen wir solche, die sich auf die Dokumentation, Transkription und Analyse authentischer Diskurse stützen. Wir beziehen uns hier im wesentlichen auf Fortbildungen im beruflichen Bereich und beschränken uns auf solche, die mündliche Kommunikationsformen zum Gegenstand haben. Maßnahmen für die schriftliche Kommunikation ("Schreibseminare") werden hier also nicht berücksichtigt. Im ersten Teil werden wir allgemeine Merkmale diskursanalytischer Fortbildungskonzepte vorstellen; im zweiten Teil folgt dann eine Darstellung des Standardverlaufs, nach dem diskursanalytische Fortbildung konzipiert und durchgeführt wird.
Wir wollen im folgenden das Verfahren der Simulation authentischer Fälle (SAF) etwas ausführlicher vorstellen. Es handelt sich um eine Methode, die das Potential diskursanalytischer Trainingskonzeptionen in spezifischer Weise nutzt und die wir bereits mehrfach mit Erfolg verwendet haben. Sie verbindet die Zwecke und Möglichkeiten traditioneller Simulationen, Plan- und Rollenspiele mit spezifischen diskursanalytischen Methoden und deren Vorteilen. Das Verfahren SAF und seine Zwecke werden zunächst allgemein charakterisiert. Dann wollen wir am Beispiel unseres Seminars, das wir 1995 durchgeführt haben, illustrieren, wie wir konkret vorgegangen sind. Schließlich werden einige weitergehende methodische Fragen diskutiert.
BACKGROUND: Parkinson's disease (PD), the second most frequent neurodegenerative disorder at old age, can be caused by elevated expression or the A53T missense mutation of the presynaptic protein alpha-synuclein (SNCA). PD is characterized pathologically by the preferential vulnerability of the dopaminergic nigrostriatal projection neurons. METHODOLOGY/PRINCIPAL FINDINGS: Here, we used two mouse lines overexpressing human A53T-SNCA and studied striatal dysfunction in the absence of neurodegeneration to understand early disease mechanisms. To characterize the progression, we employed young adult as well as old mice. Analysis of striatal neurotransmitter content demonstrated that dopamine (DA) levels correlated directly with the level of expression of SNCA, an observation also made in SNCA-deficient (knockout, KO) mice. However, the elevated DA levels in the striatum of old A53T-SNCA overexpressing mice may not be transmitted appropriately, in view of three observations. First, a transcriptional downregulation of the extraneural DA degradation enzyme catechol-ortho-methytransferase (COMT) was found. Second, an upregulation of DA receptors was detected by immunoblots and autoradiography. Third, extensive transcriptome studies via microarrays and quantitative real-time RT-PCR (qPCR) of altered transcript levels of the DA-inducible genes Atf2, Cb1, Freq, Homer1 and Pde7b indicated a progressive and genotype-dependent reduction in the postsynaptic DA response. As a functional consequence, long term depression (LTD) was absent in corticostriatal slices from old transgenic mice. CONCLUSIONS/SIGNIFICANCE: Taken together, the dysfunctional neurotransmission and impaired synaptic plasticity seen in the A53T-SNCA overexpressing mice reflect early changes within the basal ganglia prior to frank neurodegeneration. As a model of preclinical stages of PD, such insights may help to develop neuroprotective therapeutic approaches.
Die vorliegende Arbeit untersuchte die Chancen und Restriktivitäten einer künstlerischen Ausbildung. Welche Möglichkeiten stehen einer künstlerischen Ausbildung zur Verfügung und welchen Grenzen steht sie unüberwindlich gegenüber? Diese waren konstitutionstheoretisch zu entfalten und wissenschaftspraktisch anhand von mir erhobenem Datenmaterial (vornehmlich Interviews mit Studenten und Professoren von Kunsthochschulen in Deutschland) zu belegen bzw. zu verdichten...
Aus dem niedersächsischen Brutgebiet Esterweger Dose wurden von 2003 bis 2006 18 Eier aus nicht oder nur teilweise geschlüpften Gelegen sowie die Lebern eines Embryos und eines Kükens des Goldregenpfeifers auf Rückstände an Umweltchemikalien untersucht. Die Organohalogene (HCB, Σ PCB, Σ HCH, Σ DDT, Σ Chlordane und Nonachlore) sowie das Schwermetall Quecksilber wurden in sehr geringen Konzentrationen nachgewiesen. Nur die Leber des Embryos wies sehr hohe Konzentrationen an DDT und Metaboliten auf. Im Vergleich zur Kontamination der Eier anderer Watvogelarten sind die Konzentrationen der Umweltchemikalien in Goldregenpfeifereiern der Esterweger Dose als gering und den Reproduktionserfolg nicht gefährdend einzustufen.
Antibiotic treatment of tuberculosis (TB) is complex, lengthy, and can be associated with various adverse effects. As a result, patient compliance often is poor, thus further enhancing the risk of selecting multi-drug resistant bacteria. Macrophage mannose receptor (MMR)-positive alveolar macrophages (AM) constitute a niche in which Mycobacterium tuberculosis replicates and survives. Therefore, we encapsulated levofloxacin in lipid nanocarriers functionalized with fucosyl residues that interact with the MMR. Indeed, such nanocarriers preferentially targeted
MMR-positive myeloid cells, and in particular, AM. Intracellularly, fucosylated lipid nanocarriers favorably delivered their payload into endosomal compartments, where mycobacteria reside. In an in vitro setting using infected human primary macrophages as well as dendritic cells, the encapsulated antibiotic cleared the pathogen more efficiently than free levofloxacin. In conclusion, our results point towards carbohydrate-functionalized nanocarriers as a promising tool for improving TB treatment by targeted delivery of antibiotics.
Background: Surgical methods have profited from the exchange of knowledge among different specialties. Endoscopy which was introduced by gynecologists, surgeons, and internists is used now by all disciplines, and most of yesterday's laparotomies have now endoscopic alternatives. However, laparotomies are still needed, and there is no agreement among surgeons about what is the optimal abdominal incision. The Joel-Cohen incision which is used by gynecologists and obstetricians could become a valid alternative to the methods in use.
Method: The Joel-Cohen Method, which was evolved for abdominal hysterectomy is described here in detail. Only two instruments are used to open the abdomen, usually with no need for hemostasis.
Conclusion: The Joel-Cohen incision is suggested as a valid alternative for any emergency or elective surgical or urological abdominal operation. Its benefits are short operation time diminished blood loss and less need for analgesics.
Tumor antigen-specific redirection of cytotoxic T cells (CTLs) or natural killer (NK) cells including chimeric antigen receptor (CAR-) and T cell receptor (TCR-) cell therapy is currently being evaluated in different tumor entities including melanoma. Expression of melanoma-specific antigen recognized by the respective CAR or TCR directly or presented by HLA molecules is an indispensable prerequisite for this innovative therapy. In this study, we investigated in 168 FFPE tumor specimens of patients with stage I-IV melanoma the protein expression of HER2, TRP2, ABCB5, gp100, p53, and GD2 by immunohistochemistry (IHC). These results were correlated with clinical parameters. Membrane expression of HER2 and GD2 was also investigated in ten melanoma cell lines by flow cytometry for which corresponding tumors were analyzed by IHC. Our results demonstrated that gp100 was the most frequently overexpressed protein (61%), followed by TRP2 (50%), GD2 (38%), p53 (37%), ABCB5 (17%), and HER2 (3%). TRP2 expression was higher in primary tumors compared to metastases (p = 0.005). Accordingly, TRP2 and ABCB5 expression was significantly associated with lower tumor thickness of the primary (p = 0.013 and p = 0.025). There was no association between protein expression levels and survival in advanced melanoma patients. Flow cytometric analysis revealed abundant surface expression of GD2 and HER2 in all melanoma cell lines. The discordant HER2 expression in situ and in vitro suggests a tissue culture associated induction. In summary, our data support the use of gp100 and GD2 as a potential target for developing engineered TCR- or CAR-cell therapies, respectively, against melanoma.
Background: The potential anti-cancer effects of mammalian target of rapamycin (mTOR) inhibitors are being intensively studied. To date, however, few randomised clinical trials (RCT) have been performed to demonstrate anti-neoplastic effects in the pure oncology setting, and at present, no oncology endpoint-directed RCT has been reported in the high-malignancy risk population of immunosuppressed transplant recipients. Interestingly, since mTOR inhibitors have both immunosuppressive and anti-cancer effects, they have the potential to simultaneously protect against immunologic graft loss and tumour development. Therefore, we designed a prospective RCT to determine if the mTOR inhibitor sirolimus can improve hepatocellular carcinoma (HCC)-free patient survival in liver transplant (LT) recipients with a pre-transplant diagnosis of HCC. Methods: The study is an open-labelled, randomised, RCT comparing sirolimus-containing versus mTOR-inhibitor-free immunosuppression in patients undergoing LT for HCC. Patients with a histologically confirmed HCC diagnosis are randomised into 2 groups within 4-6 weeks after LT; one arm is maintained on a centre-specific mTOR-inhibitor-free immunosuppressive protocol and the second arm is maintained on a centre-specific mTOR-inhibitor-free immunosuppressive protocol for the first 4-6 weeks, at which time sirolimus is initiated. A 3-year recruitment phase is planned with a 5-year follow-up, testing HCC-free survival as the primary endpoint. Our hypothesis is that sirolimus use in the second arm of the study will improve HCC-free survival. The study is a non-commercial investigator-initiated trial (IIT) sponsored by the University Hospital Regensburg and is endorsed by the European Liver and Intestine Transplant Association; 13 countries within Europe, Canada and Australia are participating. Discussion: If our hypothesis is correct that mTOR inhibition can reduce HCC tumour growth while simultaneously providing immunosuppression to protect the liver allograft from rejection, patients should experience less post-transplant problems with HCC recurrence, and therefore could expect a longer and better quality of life. A positive outcome will likely change the standard of posttransplant immunosuppressive care for LT patients with HCC. (trial registered at www.clinicaltrials.gov: NCT00355862) (EudraCT Number: 2005-005362-36)