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Zusammenfassung Hintergrund und Zielstellung Zahlreiche Studien belegen, dass Psychotherapie wirkt. Sie findet in unterschiedlichsten Settings statt, die Datenlage dazu ist derzeit in Österreich noch ausbaufähig. Verhaltenstherapie stellt im 6‑wöchigen Kurzzeit-Setting der vorgestellten ambulanten medizinisch-psychiatrischen Rehabilitation das zentrale Behandlungselement dar und wird in Hinblick auf Wirksamkeit und Nachhaltigkeit evaluiert. Die Bewertung basiert auf „Patient reported Outcomes“. Weil mehr als ¾ der RehabilitandInnen von einer depressiven Erkrankung betroffen sind, wird das Beck Depressionsinventar als primary Outcome gewählt. Methodik Die Befragung erfolgt schriftlich bei Behandlungs-Beginn und -Ende sowie ein Jahr danach. Von 837 PatientInnen (64 % weiblich, ø 45,25 Jahre alt) leiden 76,6 % unter einer depressiven Erkrankung, dabei haben 47,2 % einen chronischen und 29,4 % einen nicht-chronischen Verlauf. Ergebnisse Differenziert nach Ausgangsbelastung zeigen sich ein Jahr nach Behandlungsende große, aber unterschiedliche Effekte. Bei PatientInnen mit stärkerer Ausgangssymptomatik finden sich größere Effekte. Die Nachhaltigkeit ist jedoch bei chronifizierten PatientInnen etwas geringer. Ein Fünftel der PatientInnen erfüllt bei Behandlungsende und ein Jahr später das Kriterium der klinischen Signifikanz und kann als „geheilt“ klassifiziert werden. Zusätzlich sind am Ende der Behandlung 23 % und ein Jahr später 18 % signifikant gebessert. Bei einem kleinen Teil kommt es zu Verschlechterungen, diesen PatientInnen sollte verstärkt Aufmerksamkeit geschenkt werden. Fazit Verhaltenstherapeutische Gruppen- und Einzeltherapien in Kombination mit weiteren therapeutischen Angeboten in der ambulanten psychiatrischen Rehabilitation sind nachhaltig wirksam. Auch wenn ein Jahr nach Ende der Behandlung bei anfangs stark depressiven RehabilitandInnen immer noch große Effekte nachweisbar sind, zeigt sich die dringende Notwendigkeit einer nachfolgenden psychotherapeutischen Begleitung im niedergelassenen Bereich oder im Rahmen der Phase 3 Rehabilitation.

Zusammenfassung Gegenstand und Ziel Hohe Druckbelastungen der Rinderklauen führen regelmäßig zu Schäden an den Klauengeweben und nachfolgend zu therapiebedürftigen Rusterholz’schen Sohlengeschwüren (RSG). Ein komplizierter Verlauf der RSG kann durch fachgerechte Klauenpflege verhindert werden. In dieser Studie wurde untersucht, wie sich ein an der Außenklaue der Hintergliedmaße vorgenommener stufenloser und keilförmiger Entlastungsschnitt vom Ballen bis zur Sohlenspitze auf die Druckverteilung unter den Klauen der Beckengliedmaße auswirkt und ob eine Veränderung der Druckverteilung zur Lederhautentlastung im Bereich des Defekts führt. Material und Methode Neunzehn isolierte distale Rindergliedmaßen vom Schlachthof (A: unbearbeiteter Zustand) wurden schrittweise bearbeitet (B: funktionelle Klauenpflege, Schritt 1–3; C: Erweiterung der Hohlkehlung und kreisrunde Bohrung zur Simulation eines RSG an der Außenklaue; D: keilförmiger Entlastungsschnitt vom Ballen bis zur Hälfte der Sohlenfläche in Richtung Sohlenspitze; E: keilförmige Erweiterung des Entlastungsschnittes über die gesamte Sohlenfläche bis kurz vor die Sohlenspitze). Zwischen den einzelnen Bearbeitungsschritten wurden die Gliedmaßen mit 200 kg belastet. Die Druckverteilung unter den Klauen wurde mit Drucksensoren gemessen. Außerdem wurden die Klauen auf einer Glasplatte positioniert, was die Beurteilung der Vorwölbung der Lederhaut bzw. des Fettpolsters anhand des Bohrlochs ermöglichte. Ergebnisse In Zustand A lasteten durchschnittlich 63 %, bei Zustand E 30 % der gesamten Kraft auf der Außenklaue. Mit zunehmender Bearbeitung der Klauen verlagerten sich die Druckmaxima vom Ballen- in den Sohlenspitzenbereich. Die relative Belastungsfläche der Innenklaue nahm mit fortschreitender Bearbeitung um bis zu 18,4 % zu. In Zustand E ergab sich im Vergleich zu C eine signifikante Reduzierung der Lederhautvorwölbung im Bereich des künstlichen Sohlendefekts. Schlussfolgerung Der keilförmige Entlastungsschnitt (E) führte an den isolierten Rindergliedmaßen zu einer Außenklauen- und Ballenentlastung und stellt eine Methode zur Defekt- und Lederhautentlastung dar. Klinische Relevanz Der Entlastungsschnitt könnte auch am lebenden Tier eine Druckentlastung der Außenklaue bewirken und so den Krankheitsverlauf von RSG positiv beeinflussen.

Zusammenfassung Hintergrund Zur Bewertung des Behandlungserfolgs bei depressiven Symptomen stehen unterschiedliche statistische Methoden zur Verfügung. Effektgrößen, prozentuale Verbesserung, signifikante Verbesserung und klinisch signifikante Verbesserung sind gängige Methoden zur Bewertung von Behandlungsergebnissen basierend auf „Patient Reported Outcomes“. Fragestellung Wie unterscheiden sich die Behandlungsergebnisse in Abhängigkeit von der verwendeten Methode? Methodik Für N = 3018 Patienten einer ambulanten psychiatrischen Rehabilitationsklinik wurden Verbesserungen anhand von Effektgrößen, prozentuellen Veränderungen, signifikanten und klinisch signifikanten Veränderungen im Beck Depressions-Inventar (BDI-II) berechnet. Ergebnisse Für die Gesamtgruppe zeigt sich ein gut mittlerer Effekt von d = 0,62, der nach Ausschluss von zum Zeitpunkt der Aufnahme nicht depressiven (euthymen) Patienten als groß bewertet werden kann (d = 0,79). Die stärkste Aussagekraft für die Symptomreduktion der Depression hat die Methode der klinischen Signifikanz, bei einem Cut-off von 13 Punkten wurden 23 % als klinisch signifikant und weitere 19,3 % als signifikant gebessert klassifiziert. Bei der Methode der prozentuellen Verbesserung erreichten 30,4 % der Patienten einen Wert von mindestens 50 %. Schlussfolgerungen Effektgrößen geben einen groben Überblick über den Behandlungserfolg eines Patientenkollektivs ohne Berücksichtigung des Endzustands und der Variabilität innerhalb des Kollektivs. Die prozentuelle Veränderung scheint eher für die Kontrolle des Ansprechens auf eine Behandlung geeignet zu sein. Ergebnisse zur klinischen Signifikanz geben am transparentesten Auskunft über signifikante Verbesserungen und den Wechsel vom dysfunktionalen in den funktionalen Bereich.

Genetic factors were shown to play a major role in both variation of treatment response and incidence of adverse effects to medication in affective disorders. Nevertheless, there is still a lack of therapygenetic studies, investigating the prediction of psychological therapy outcomes from genetic markers. Neuroplasticity and one of its mediators, brain-derived neurotrophic factor (BDNF), are potential research targets in this field. We aimed to investigate Tag SNP polymorphisms of the BDNF gene in depressed patients treated with cognitive behavioral therapy (CBT) in the context of a standardized 6-weeks outpatient rehabilitation program. Treatment response was assessed calculating the mean differences in BDI-II (Beck Depression Inventory) scores from admission to discharge. Six BDNF SNPs, including the Val66Met polymorphism (rs6265), were genotyped. Both genotypic data and BDI-II-scores at admission and discharge were available for 277 patients. Three SNPs, rs10501087 (p = 0.005, FDRp=0.015), rs11030104 (p = 0.006, FDRp=0.012), and the Val66Met polymorphism (rs6265, p0.001, FDRp=0.006), were significantly associated with treatment response in depressed patients, even after multiple testing correction using the false discovery rate method (FDRp). We conclude that BDNF might serve as promising genetic marker for treatment response to psychological treatment in depression. However, due to our limited sample size, further studies are needed to disentangle the role of BDNF as potential therapygenetic marker.

Background Oxytocin (OXT) is a neuropeptide and hormone involved in emotional functioning and also seems to play a role in moderating the stress response. Both preclinical and clinical studies point to an increased methylation status of the Oxytocin receptor (OXTR) promoter region with concomitant deficits in social, cognitive and emotional functioning. We hypothesize that methylation levels (%) of the oxytocin receptor promoter region correlate with the severity of depression symptoms and/or with the severity of childhood trauma within this present sample of affective disorder patients. Methodology Eight hundred forty six (846) affective disorder patients of Central European origin were recruited at the Department of Psychiatry and Psychotherapy of the Medical University Vienna, the Karl Landsteiner University for Health and Science and Zentren für seelische Gesundheit, BBRZ-Med Leopoldau. Psychiatric assessment included a semi-structured diagnostic interview (Schedules for Clinical Assessment in Neuropsychiatry), the Hamilton Depression Scale and the Childhood Trauma Questionnaire. Concomitantly DNA samples of peripheral blood cells were collected for Multiplexed and Sensitive DNA Methylation Testing. Results Our data suggests a positive but not significant association between OXTR promoter Exons 1–3 methylation levels and severity of depression symptoms as well as severity of emotional neglect in affective disorder patients and no association with childhood trauma. Conclusions Our findings contribute to elucidate the role of OXTR in affective disorders, but further longitudinal studies in particular are necessary to broaden the current state of knowledge.

Street dust is a major source of pollution and exposure of residents of West Africa to toxic chemicals. There is however, limited knowledge about the chemical composition and sources of street dust in urban areas of sub-Saharan Africa. The total carbon (TC), nitrogen (TN), sulfur (TS) and the stable carbon isotope ratios (δ13C) contents of street dust sampled from 25 sites distributed across Kumasi (a metropolis in Ghana with a population of ca. 2 million) were determined. In addition, black carbon (BC) and their subunits (soot and char) in these samples were also determined. The concentrations of TC, TN and TS in the dusts were 5–71 mg g−1, 0.3–4.3 mg g−1 and 0.2–1.4 mg g−1, respectively. The concentrations of TC, TN and TS were higher than at the background site of the metropolis by a factor of 5.1 (range: 1.7–12), 3.9 (1.1–13) and 2.8 (0.7–5), respectively. The BC, char and soot concentrations in these samples averaged 1.6 mg g−1 (0.13–4.4), 1.2 mg g−1 (0.08–3.7) and 0.36 mg g−1 (0.05–1.5), respectively. The concentrations of BC, char and soot in the street dust were higher than in the background location by factors of 5 (range: 0.8–13), 6 (0.7–17) and 3 (0.5–12), respectively. The TC, TN, TS, BC, soot and char concentrations were positively correlated with each other and with polycyclic aromatic compounds (PAHs, oxygenated PAHs and azaarenes from a previous study), indicating their common origin and fate. The δ13C values ranged from −27 to −24 [‰], with more polluted sites being more depleted in 13C. Based on the chemical composition of the street dusts, the 25 sites could be clustered into four groups by hierarchical cluster analysis which reflect areas of varying anthropogenic influence and, accordingly, exposure to hazardous chemicals.

Overloading or excessive mechanical stress to the claws may damage the sensitive claw tissues and subsequently lead to sole ulcers. Corrective treatment can prevent complications of these sole ulcers. The aim of this study was to investigate the effects of a wedge-shaped relief incision from the bulb to the tip of the outer claw of the pelvic limb on the pressure distribution beneath the pertaining claw. Furthermore, it aimed to clarify whether a change in the pressure distribution would lead to dermal pressure relief in the area of a horn defect.Nineteen isolated bovine limbs from an abattoir were gradually trimmed resulting in following stages. A: initial condition; B: functional claw trimming, steps 1-3; C: extension of the model and drill of a circular lesion at the Rusterholz site (outer claw ulcer simulation); D: wedge shaped, weight-relieving incision from the bulb halfway towards the sole tip; E: further extension of the wedge-shaped incision towards the sole tip. The limbs were loaded with 200 kg following each of the procedures. A pressure sensor system was used in order to analyze the pressure distribution beneath the claws. Furthermore, positioning of the claws on a glass plate allowed for an evaluation of corium resp. fat cushion protrusion through the artificial lesion.In the untrimmed claws, an average of 63 % of the total force applied rested on the outer claw area. This value decreased to 30 % following step E. Maximum pressure values shifted from the bulb area towards the sole tip with increasing degree of claw trimming. The relative loading area of the inner claw increased to up to 18.4 % following the procedures. The described incision technique (step E) resulted in a significant reduction of corium protrusion through the artificial horn defect in comparison to the claw situation in step C.The wedge-shaped, weight-relieving incision (step E) led to pressure reduction in the area of the outer claw and the bulb region in this ex-vivo-study. Therefore, this trimming method may serve to relieve pressure from the vulnerable Rusterholz site as well as providing means for reducing corium compression.The described trimming method facilitates pressure relief on the outer claw area in live animals. In this, it may exert a positive effect on disease progression in Rusterholz sole ulcers.Hohe Druckbelastungen der Rinderklauen führen regelmäßig zu Schäden an den Klauengeweben und nachfolgend zu therapiebedürftigen Rusterholz’schen Sohlengeschwüren (RSG). Ein komplizierter Verlauf der RSG kann durch fachgerechte Klauenpflege verhindert werden. In dieser Studie wurde untersucht, wie sich ein an der Außenklaue der Hintergliedmaße vorgenommener stufenloser und keilförmiger Entlastungsschnitt vom Ballen bis zur Sohlenspitze auf die Druckverteilung unter den Klauen der Beckengliedmaße auswirkt und ob eine Veränderung der Druckverteilung zur Lederhautentlastung im Bereich des Defekts führt.Neunzehn isolierte distale Rindergliedmaßen vom Schlachthof (A: unbearbeiteter Zustand) wurden schrittweise bearbeitet (B: funktionelle Klauenpflege, Schritt 1–3; C: Erweiterung der Hohlkehlung und kreisrunde Bohrung zur Simulation eines RSG an der Außenklaue; D: keilförmiger Entlastungsschnitt vom Ballen bis zur Hälfte der Sohlenfläche in Richtung Sohlenspitze; E: keilförmige Erweiterung des Entlastungsschnittes über die gesamte Sohlenfläche bis kurz vor die Sohlenspitze). Zwischen den einzelnen Bearbeitungsschritten wurden die Gliedmaßen mit 200 kg belastet. Die Druckverteilung unter den Klauen wurde mit Drucksensoren gemessen. Außerdem wurden die Klauen auf einer Glasplatte positioniert, was die Beurteilung der Vorwölbung der Lederhaut bzw. des Fettpolsters anhand des Bohrlochs ermöglichte.In Zustand A lasteten durchschnittlich 63 %, bei Zustand E 30 % der gesamten Kraft auf der Außenklaue. Mit zunehmender Bearbeitung der Klauen verlagerten sich die Druckmaxima vom Ballen- in den Sohlenspitzenbereich. Die relative Belastungsfläche der Innenklaue nahm mit fortschreitender Bearbeitung um bis zu 18,4 % zu. In Zustand E ergab sich im Vergleich zu C eine signifikante Reduzierung der Lederhautvorwölbung im Bereich des künstlichen Sohlendefekts.Der keilförmige Entlastungsschnitt (E) führte an den isolierten Rindergliedmaßen zu einer Außenklauen- und Ballenentlastung und stellt eine Methode zur Defekt- und Lederhautentlastung dar.Der Entlastungsschnitt könnte auch am lebenden Tier eine Druckentlastung der Außenklaue bewirken und so den Krankheitsverlauf von RSG positiv beeinflussen.

Performance of a proton exchange membrane fuel cell (PEMFC) is significantly determined by the structure and composition of the electrode layer. Electrode layers are formed from inks consisting of platinum-doped carbon black particles, perfluorosulfonic acid (PFSA) ionomer and a dispersing solvent. Interaction between these materials mainly influences suspension stability, ionomer conformation and therewith layer morphology. We characterize the interplay between a short sidechain (SSC) PFSA ionomer (Aquivion® D79-25BS) and a solvent mixture (diacetone alcohol (DAA) and water with different weight ratios) by using Hansen solubility/dispersibility parameters (HSP) and by experimental tests. It was found that HSPs are well suitable to describe the ionomer/solvent interactions. In particular, the HSP difference in terms of the hydrogen bonds is responsible for the poor affinity between ionomer and solvent at low DAA concentrations. With increasing DAA content the affinity between ionomer and solvent increases as indicated by better matching HSPs. For an ionomer concentration of 4 wt%, Aquivion always forms molecular solutions for all DAA-in-water mixing ratios. Self-organization of the ionomer molecules changes from densely packed/collapsed molecules with highly deprotonated sulfonic acid side groups at low DAA concentrations to unfolded Aquivion molecules with a low dissociation degree of the sulfonic acid groups at high DAA concentrations.

This phase 1 trial (NCT01938846) determined the maximum tolerated dose (MTD) of the mTOR serine/threonine kinase inhibitor, BI 860585, as monotherapy and with exemestane or paclitaxel in patients with advanced solid tumors. This 3+3 dose-escalation study assessed BI 860585 monotherapy (5&ndash, 300 mg/day, Arm A), BI 860585 (40&ndash, 220 mg/day, Arm B) with 25 mg/day exemestane, and BI 860585 (80&ndash, Arm C) with 60&ndash, 80 mg/m2/week paclitaxel, in 28-day cycles. Primary endpoints were the number of patients with dose-limiting toxicities (DLTs) in cycle 1 and the MTD. Forty-one, 25, and 24 patients were treated (Arms A, B, and C). DLTs were observed in four (rash (n = 2), elevated alanine aminotransferase/aspartate aminotransferase, diarrhea), four (rash (n = 3), stomatitis, and increased gamma-glutamyl transferase), and two (diarrhea, increased blood creatine phosphokinase) patients in cycle 1. The BI 860585 MTD was 220 mg/day (Arm A) and 160 mg/day (Arms B and C). Nine patients achieved an objective response (Arm B: Four partial responses (PRs), Arm C: Four PRs, one complete response). The disease control rate was 20%, 28%, and 58% (Arms A, B, and C). The most frequent treatment-related adverse events (AEs) were hyperglycemia (54%) and diarrhea (39%) (Arm A), diarrhea (40%) and stomatitis (40%) (Arm B), fatigue (58%) and diarrhea (58%) (Arm C). The MTD was determined in all arms. Antitumor activity was observed with BI 860585 monotherapy and in combination with exemestane or paclitaxel.

This study had as a general objective to understand how the recognition of the teaching work in the childhood education interferes with the health of the teachers. For this purpose, it sought to understand the changes in the context of childhood education and the factors that produce pleasure and suffering due to the work environment. The research was carried out in a municipality in the countryside of Rio Grande do Sul, with eight teachers from the first stage of public education, through semi-structured interviews. The methodology used was an adaptation of the Psychodynamics of Work Stricto Sensu. Teaching work in childhood education has undergone changes, its organization included. Some teachers had to assume the pedagogical responsibility of more than one class, which has led to an increase in the workload. In addition, they have little time with the children and the main activity refers to tasks distribution. In this sense, the dynamic of contribution and recognition of the professionals is affected. The acknowledgment is essential so that the work has a meaning for the subject. For the researched teachers, it comes from the children with whom they work, manifested through affection.

As the phylogenetic organization of mammalian polyomaviruses is complex and currently incompletely resolved, we aimed at a deeper insight into their evolution by identifying polyomaviruses in host orders and families that have either rarely or not been studied. Sixteen unknown and two known polyomaviruses were identified in animals that belong to 5 orders, 16 genera, and 16 species. From 11 novel polyomaviruses, full genomes could be determined. Splice sites were predicted for large and small T antigen (LTAg, STAg) coding sequences (CDS) and examined experimentally in transfected cell culture. In addition, splice sites of seven published polyomaviruses were analyzed. Based on these data, LTAg and STAg annotations were corrected for 10/86 and 74/86 published polyomaviruses, respectively. For 25 polyomaviruses, a spliced middle T CDS was observed or predicted. Splice sites that likely indicate expression of additional, alternative T antigens, were experimentally detected for six polyomaviruses. In contrast to all other mammalian polyomaviruses, three closely related cetartiodactyl polyomaviruses display two introns within their LTAg CDS. In addition, the VP2 of Glis glis (edible dormouse) polyomavirus 1 was observed to be encoded by a spliced transcript, a unique experimental finding within the Polyomaviridae family. Co-phylogenetic analyses based on LTAg CDS revealed a measurable signal of codivergence when considering all mammalian polyomaviruses, most likely driven by relatively recent codivergence events. Lineage duplication was the only other process whose influence on polyomavirus evolution was unambiguous. Finally, our analyses suggest that an update of the taxonomy of the family is required, including the creation of novel genera of mammalian and non-mammalian polyomaviruses. info:eu-repo/semantics/publishedVersion

Objetivo: Valorar la capacidad diagnóstica y el seguimiento de las cardiopatías congénitas con diagnóstico prenatal realizadas en el Centro de Referencia Perinatal Oriente (CERPO). Método: Se analizan todas las cardiopatías congénitas con diagnóstico prenatal que ingresaron al CERPO entre abril 2003 y diciembre de 2011. Se realiza seguimiento postnatal, se evalúa la concordancia entre el diagnóstico pre y postnatal, y se compara el pronóstico con la experiencia previamente reportada en la literatura. Resultados: Se detectaron 568 cardiopatías congénitas, el 53% correspondían a pacientes referidas desde otras regiones del país. En relación a la edad materna y paterna el 28% y el 35% tenían 35 años o más, respectivamente. De las 568 cardiopatías congénitas controladas, el 75% fueron pesquisadas con la ecocardiografía por visión de 4 cámaras y el 25% por visión de tractos de salida. La concordancia entre la ecocardiografía prenatal y postnatal fue de 87%. Los diagnósticos más frecuentes correspondieron a comunicación interventricular, síndrome de hipoplasia ventricular izquierdo, arritmias y canal aurículoventricular. Se detectaron 60 cromosomopatías, 8 síndromes genéticos y 145 malformaciones extracardiacas asociadas. Se pudo realizar seguimiento de sobrevida al año en 390 pacientes, la sobrevida global en este grupo (excluidas las aneuploidías incompatibles con la vida) alcanzó un 44%. Conclusión: Existe una alta tasa de diagnóstico prenatal de cardiopatías congénitas a nivel terciario, con un 87% de concordancia entre ecocardiografía pre y postnatal. La sobrevida global de pacientes con cardiopatías congénitas fue de 44% al año de seguimiento. Por las características territoriales de nuestro país debiera contarse con más centros de referencia perinatal, al menos en las zonas norte y sur del país. Objective: To evaluate the diagnostic and follow-up congenital heart disease with prenatal diagnosis performed in the Centro de Referencia Perinatal Oriente (CERPO). Method: We analyzed all the congenital heart disease with prenatal diagnosis admitted to CERPO between April 2003 and December 2011. Postnatal follow-up is performed, evaluating the correlation between pre and postnatal diagnosis and prognosis compared with the experience previously reported in the literature. Results: We detected 568 congenital heart diseases of which 53% were patients referred from other regions of the country. In relation to maternal and paternal age, 28% and 35% were 35 years or older, respectively. From 568 controlled congenital heart diseases, 75% could be researched to ultrasound echocardiography 4-chamber view and 25% per-view outflow tracts. The correlation between prenatal and postnatal echocardiography in this series was 87%. The most frequent diagnosis was interventricular communication, hypoplastic left heart syndrome, arrhythmias and atrioventricular canal. In this series we detected 60 chromosomal, 8 genetic syndromes and 145 extracardiac malformations. Follow-up could be performed one year survival in 390 patients, overall survival in this group (excluding aneuploidies with life incompatibility) reached 44%. Conclusion: There is a high rate of prenatal diagnosis of congenital heart disease at the tertiary level, with 87% concordance between pre-and postnatal echocardiography. Overall survival of patients with congenital heart disease is 44% at one year. For the territorial characteristics of our country should be counted more perinatal referral centers, at least in the north and south.

Glaciers all over the world are expected to continue to retreat due to the global warming throughout the 21st century. Consequently, future seasonal water availability might become scarce once glacier areas have declined below a certain threshold affecting future water management strategies. Particular attention should be paid to glaciers located in a karstic environment, as parts of the meltwater can be drained by underlying karst systems, making it difficult to assess water availability. In this study tracer experiments, karst modeling and glacier melt modeling are combined in order to identify flow paths in a high alpine, glacierized, karstic environment (Glacier de la Plaine Morte, Switzerland) and to investigate current and predict future downstream water availability. Flow paths through the karst underground were determined with natural and fluorescent tracers. Subsequently, geologic information and the findings from tracer experiments were assembled in a karst model. Finally, glacier melt projections driven with a climate scenario were performed to discuss future water availability in the area surrounding the glacier. The results suggest that during late summer glacier meltwater is rapidly drained through well-developed channels at the glacier bottom to the north of the glacier, while during low flow season meltwater enters into the karst and is drained to the south. Climate change projections with the glacier melt model reveal that by the end of the century glacier melt will be significantly reduced in the summer, jeopardizing water availability in glacier-fed karst springs.

Climate and environmental reconstructions from natural archives are important for the interpretation of current climatic change. Few quantitative high-resolution reconstructions exist for South America which is the only land mass extending from the tropics to the southern high latitudes at 56°S. We analyzed sediment cores from two adjacent lakes in Northern Chilean Patagonia, Lago Castor (45°36′S, 71°47′W) and Laguna Escondida (45°31′S, 71°49′W). Radiometric dating (210Pb, 137Cs, 14C-AMS) suggests that the cores reach back to c. 900 BC (Laguna Escondida) and c. 1900 BC (Lago Castor). Both lakes show similarities and reproducibility in sedimentation rate changes and tephra layer deposition. We found eight macroscopic tephras (0.2–5.5 cm thick) dated at 1950 BC, 1700 BC, at 300 BC, 50 BC, 90 AD, 160 AD, 400 AD and at 900 AD. These can be used as regional time-synchronous stratigraphic markers. The two thickest tephras represent known well-dated explosive eruptions of Hudson volcano around 1950 and 300 BC. Biogenic silica flux revealed in both lakes a climate signal and correlation with annual temperature reanalysis data (calibration 1900–2006 AD; Lago Castor r = 0.37; Laguna Escondida r = 0.42, seven years filtered data). We used a linear inverse regression plus scaling model for calibration and leave-one-out cross-validation (RMSEv = 0.56 °C) to reconstruct sub decadal-scale temperature variability for Laguna Escondida back to AD 400. The lower part of the core from Laguna Escondida prior to AD 400 and the core of Lago Castor are strongly influenced by primary and secondary tephras and, therefore, not used for the temperature reconstruction. The temperature reconstruction from Laguna Escondida shows cold conditions in the 5th century (relative to the 20th century mean), warmer temperatures from AD 600 to AD 1150 and colder temperatures from AD 1200 to AD 1450. From AD 1450 to AD 1700 our reconstruction shows a period with stronger variability and on average higher values than the 20th century mean. Until AD 1900 the temperature values decrease but stay slightly above the 20th century mean. Most of the centennial-scale features are reproduced in the few other natural climate archives in the region. The early onset of cool conditions from c. AD 1200 onward seems to be confirmed for this region.

Accurate projections of future climate changes in regions susceptible to drought depend on a good understanding of past climate changes and the processes driving them. In the absence of longer term instrumental data, paleoclimate data are needed. In this study we develop a precipitation reconstruction for Rebecca Lagoon (41°11′S, 144°41′E), northwest Tasmania. First, the relationship between scanning reflectance spectroscopy measurements of sediment cores in the visible spectrum (380–730 nm) and instrumental precipitation record (1912–2009) was used to develop a model to reconstruct precipitation back in time. Results showed that the ratio of reflectance between 660 and 670 nm (i.e., reflectance at 660 nm/reflectance at 670 nm; a measure of pigment diagenesis) was significantly related to annual precipitation. A calibration model was developed (R = − 0.56, pauto < 0.001, RMSEP = 43.0 mm yr− 1, 5 year triangular filtered data, calibration period 1912–2009). Second, this calibration-in-time model was used to reconstruct late Holocene precipitation changes over the last ~ 3000 years. This showed relatively dry conditions from ca. 3100–2800 cal yr BP, wet conditions from ca. 2800–2400 cal yr BP, dry conditions from ca. 2400–2000 calyr BP, and variable conditions after this. Relatively wet conditions occurred from ca. 500 cal yr BP to the late AD 1800 s (ca. 50 cal. yr BP). The precipitation reconstruction indicates that conditions were relatively dry for the 20th century compared to the last ~ 3000 years. In particular, the dry period measured in recent decades is one of the most intense in at least the last 500 years. As precipitation in this region is primarily driven by the Southern Hemisphere westerly winds, these changes are discussed in terms of shifts in westerly wind strength and/or position.

Morphogenesis of human cytomegalovirus (HCMV) is still only partially understood. We have characterized the role of HCMV tegument protein pUL71 in viral replication and morphogenesis. By using a rabbit antibody raised against the C terminus of pUL71, we could detect the protein in infected cells, as well as in virions showing a molecular mass of approximately 48 kDa. The expression of pUL71, detected as early as 48 h postinfection, was not blocked by the antiviral drug foscarnet, indicating an early expression. The role of pUL71 during virus replication was investigated by construction and analysis of a UL71 stop mutant (TBstop71). The mutant could be reconstituted on noncomplementing cells proving that pUL71 is nonessential for virus replication in human fibroblasts. However, the inhibition of pUL71 expression resulted in a severe growth defect, as reflected by an up to 16-fold reduced extracellular virus yield after a high-multiplicity infection and a small-plaque phenotype. Ultrastructural analysis of cells infected with TBstop71 virus revealed an increased number of nonenveloped nucleocapsids in the cytoplasm, many of them at different stages of envelopment, indicating that final envelopment of nucleocapsids in the cytoplasm was affected. In addition, enlarged multivesicular bodies (MVBs) were found in close proximity to the viral assembly compartment, suggesting that pUL71 affects MVBs during virus infection. The observation of numerous TBstop71 virus particles attached to MVB membranes and budding processes into MVBs indicated that these membranes can be used for final envelopment of HCMV.

Aggregation of the microtubule-associated protein tau into neurofibrillary tangles is the pathological hallmark of a variety of dementias. For reasons not yet known, tau becomes excessively phosphorylated in Alzheimer's brains and as a result no longer binds properly to microtubules. Here we studied the impact of phosphorylation on the conformational and binding properties of the repeat region of tau (K18) that is necessary for microtubule assembly and forms the core of paired helical filaments. To mimic phosphorylation, we introduced four mutations of serine to glutamate residues at positions 262, 293, 324, and 356. NMR spectroscopy demonstrates that pseudophosphorylation at these sites modifies the structural properties in repeats 1 and 2, in particular for Gln265-Lys267. Gln265-Lys267 are in close proximity to Ser262, the phosphorylation site that most strongly attenuates binding to microtubules. In contrast, the pseudophosphorylation mimic of tau efficiently interacts with the polyanion heparin. Thus, phosphorylation of the repeat region of natively unfolded tau induces specific conformational changes that have a strong impact on its biological function and involvement in disease.

DNA polymerase selectivity is crucial for the survival of any living species, yet varies significantly among different DNA polymerases. Errors within DNA polymerase-catalyzed DNA synthesis result from the insertion of noncanonical nucleotides and extension of misaligned DNA substrates. The substrate binding characteristics among DNA polymerases are believed to vary in properties such as shape and tightness of the binding pocket, which might account for the observed differences in fidelity. Here, we employed 4'-alkylated nucleotides and primer strands bearing 4'-alkylated nucleotides at the 3'-terminal position as steric probes to investigate differential active site properties of human DNA polymerase beta (Pol beta) and the 3'-->5'-exonuclease-deficient Klenow fragment of E. coli DNA polymerase I (KF(exo-)). Transient kinetic measurements indicate that both enzymes vary significantly in active site tightness at both positions. While small 4'-methyl and -ethyl modifications of the nucleoside triphosphate perturb Pol beta catalysis, extension of modified primer strands is only marginally affected. Just the opposite was observed for KF(exo-). Here, incorporation of the modified nucleotides is only slightly reduced, whereas size augmentation of the 3'-terminal nucleotide in the primer reduces the catalytic efficiency by more than 7000- and 260,000-fold, respectively. NMR studies support the notion that the observed effects derive from enzyme substrate interactions rather than inherent properties of the modified substrates. These findings are consistent with the observed differential capability of the investigated DNA polymerases in fidelity such as processing misaligned DNA substrates. The results presented provide direct evidence for the involvement of varied steric effects among different DNA polymerases on their fidelity.

In the western world, more than 80 million people decorate their skin with tattoos. Tattoo colorants are injected into the skin, like medical drugs. Most tattoo colorants are industrial pigments, and chemical industries have never produced them for human use but only to stain consumer goods. Up to 10% of tattooed people request removal of their tattoos because of an improved self-image or social stigmatization. In contrast to tattooing, physicians usually perform the tattoo removal. For that purpose laser light at very high intensities irradiates the skin to destroy the tattoo pigments. Based on a recent analysis of tattoo pigments, two widely used azo compounds were irradiated in suspension with laser and subsequently analyzed by using quantitative high-performance liquid chromatography and mass spectrometry. The high laser intensities cleaved the azo compounds, leading to an increase of decomposition products such as 2-methyl-5-nitroaniline, 2-5-dichloraniline and 4-nitro-toluene, which are toxic or even carcinogenic compounds. Moreover, the results of the chemical analysis show that the tattoo colorants already contain such compounds before laser irradiation. Because of a high number of patients undergoing laser treatment of tattoos and based on the results of our findings in vitro, it is an important goal to perform a risk assessment in humans regarding laser-induced decomposition products.

Background HCV RNA is commonly recognized as key parameter for reliable diagnosis and treatment monitoring of HCV infection. Determination of blood HCV RNA concentrations reduces the pre-seroconversion period in the diagnosis of HCV infection and supports management of interferon alpha-based therapies of chronic HCV infection. Objectives and study design The COBAS ® AmpliPrep/COBAS ® TaqMan ® HCV Test combines automated extraction of nucleic acids on the COBAS ® AmpliPrep Instrument with real-time PCR on the COBAS ® TaqMan ® Analyzer, thus greatly reducing hands-on time during sample preparation and amplification/detection. The test, which is calibrated to the 1st International HCV WHO Standard, was evaluated for sensitivity, dynamic range, precision, matrix equivalence, genotype inclusivity, interfering substances, diagnostic and analytical specificity, as well as for correlation with two other commercial tests for HCV RNA quantification. Results The COBAS ® AmpliPrep/COBAS ® TaqMan ® HCV Test demonstrated a >6-log dynamic range of 43–6.90E+7 IU/mL, a sensitivity (95% hit rate) of at least 15 IU/mL for HCV WHO Standard and a comparable quantification of genotypes 1–6. HCV quantification results were in good correlation with those obtained by the COBAS ® AMPLICOR ® HCV MONITOR Test v2.0 and the VERSANT ® HCV RNA 3.0 test. Conclusions The fully automated COBAS ® AmpliPrep/COBAS ® TaqMan ® HCV Test excellently accomplishes the requirements for highly sensitive detection and reliable quantification of HCV in clinical samples and thus improves therapy monitoring and management of HCV infection.

Nachdem in Kap. 3 die Methoden des Projektrisikomanagements vorgestellt wurden, werden im Folgenden die spezifischen Anforderungen des Mittelstands an das Projektrisikomanagement abgeleitet. Daraufhin werden die genannten Methoden anhand dieser Anforderungen bewertet und ein Reifegradmodell zur Implementierung eines Projektrisikomanagements im Mittelstand entwickelt. Anschliesend wird auf die Organisation des Projektrisikomanagements im Mittelstand eingegangen.

Im Folgenden wird die Dr. Schneider Kunststoffwerke GmbH kurz vorgestellt und als mittelstandisches Unternehmen gemas Abschn. 2.3.1 eingeordnet. Darauf aufbauend wird das Unternehmen in das Reifegradmodell aus Abschn. 4.3 eingestuft. Der Fokus des funften Kapitels liegt in den Abschn. 5.3 und 5.4, die zeigen wie das Risikomanagement bei der Dr. Schneider GmbH idealerweise umgesetzt werden konnte. Der Abschn. 5.5 liefert abschliesend weitere Handlungsempfehlungen im Bereich des Projektrisikomanagement beim genannten Unternehmen.

Nachdem in Abschn. 2.2.3 die Aufgaben des Projektrisikomanagements vorgestellt wurden, werden im folgendem dritten Kapitel ausgewahlte Methoden als Losungsverfahren dieser Aufgaben aufgezeigt und kritisch diskutiert.

Residual dipolar couplings (RDCs) are applied here for the analysis of weak, transient binding events between phosphatidylcholine bilayers and polyols. Large signal responses are observed even for low percentages of 'ligand-receptor complexes', making RDCs a sensitive tool for the analysis of molecular recognition events. The different degree of alignment in solution can be compared as a result of the calculation of the alignment tensor elements. By varying polarity and/or charge of the molecules under investigation, nonspecific hydrophobic effects can be excluded.

Brain imaging techniques have provided substantial insight into the pathophysiology of hepatic encephalopathy (HE). Magnetic resonance imaging gave hint to the fact that there is an increased deposition of manganese especially in the basal ganglia. Single photon emission computed tomography (SPECT) and positron emission tomography (PET) showed that the preference of the basal ganglia might be due to differences in regional cerebral blood flow and an additional redistribution of blood flow from the cortex to subcortical regions in cirrhotics. PET studies using ammonia as tracer showed that the cerebral metabolism of ammonia and the permeability of the blood brain barrier for ammonia is increased in cirrhotic patients compared to healthy controls. The regional ammonia supply is in accordance with the regional blood flow. In accordance with these findings fluorodesoxyglucose-PET-studies of the brain in cirrhotics showed characteristic alterations of glucose utilisation in the patients with a relative decrease of the glucose utilisation of the cingulate gyrus, the frontomedial, frontolateral, and parieto-occipital cortex, while the glucose utilisation of the basal ganglia, the hippocampus, and the cerebellum was relatively increased. These findings fit well with the clinical characteristics of early stages of HE such as deficits in attention, visuo-spatial orientation, visuo-constructive abilities, motor speed, and accuracy.

Clinical and histopathological findings hint at regional differences in the brain's sensitivity to metabolic changes in cirrhosis. The aim of the present study was to examine regional differences in cerebral ammonia metabolism in patients with cirrhosis and grade 0-to-I hepatic encephalopathy (HE). 13N-ammonia, 15O-water positron emission tomography (PET) and magnetic resonance imaging (MRI) were performed. Quantitative values of cerebral blood flow (CBF) and the initial cerebral ammonia uptake rate (K1) were derived for several regions of interest from images of the desired parameters after interactive coregistration with the patients' MRI-studies. CBF (mL/mL/min), K1 (mL/mL/min), and the ammonia extraction fraction (K1/CBF) showed marked regional variance with the highest levels in the thalamus, the lenticular nucleus, and the cerebellum. In conclusion, the regional differences in cerebral ammonia uptake correspond to the distribution of histopathological changes in the brain of patients with cirrhosis as well as clinical features of HE, characterized by signs of basal ganglia and cerebellar dysfunction with corresponding signs of functional impairment, especially of the frontal cortex and cingulate gyrus. (HEPATOLOGY 2004;40:73–79.)

The high-pathogenicity island (HPI) of virulent Yersiniae consists of (i) a functional core encoding for biosynthesis and uptake of the siderophore yersiniabactin and (ii) a 5- to 13-kb AT-rich region of unknown function. This Yersinia HPI has been shown to be widely distributed among different pathotypes of Escherichia coli. In this study, the insertion site of the HPI was defined in three different E. coli strains: The enteroaggregative E. coli (EAggEC) strain 17-2, the uropathogenic (UPEC) E. coli strain 536, and the probiotic E. coli DSM6601. We demonstrated that in all three E. coli isolates the HPI is associated with the asnT tRNA (5'-extremity) and truncated in the AT-rich region (3'-extremity) since the 17-bp direct repeat (DR) of the asn tRNA that flanks the HPI in Yersinia is missing in E. coli. Moreover, in comparison to the HPI-negative E. coli K-12 strain, a uniform deletion must have taken place in the E. coli chromosome adjacent to the 3'-border of the HPI.

Sigma(S) (RpoS) is a highly unstable global regulatory protein in Escherichia coli, whose degradation is inhibited by various stress signals, such as carbon starvation, high osmolarity and heat shock. As a consequence, these stresses result in the induction of sigma(S)-regulated stress-protective proteins. The two-component-type response regulator, RssB, is essential for the rapid proteolysis of sigma(S) and is probably involved in the transduction of some of these stress signals. Acetyl phosphate can be used as a phosphodonor for the phosphorylation of various response regulators in vitro and, in the absence of the cognate sensor kinases, acetyl phosphate can also modulate the activities of several response regulators in vivo. Here, we demonstrate increased in vivo half-lives of sigma(S) and the RpoS742::LacZ hybrid protein (also a substrate for RssB-dependent proteolysis) in acetyl phosphate-free (pta-ackA) deletion mutants, even though no sensor kinase was eliminated. The in vivo data indicate that acetyl phosphate acts through the response regulator, RssB. In vitro, efficient phosphotransfer from radiolabelled acetyl phosphate to the Asp-58 residue of RssB (the expected site of phosphorylation in the RssB receiver domain) was observed. Via such phosphorylation, acetyl phosphate may thus modulate RssB activity even in an otherwise wild-type background. While acetyl phosphate is not essential for the transduction of specific environmental stress signals, it could play the role of a modulator of RssB-dependent proteolysis that responds to the metabolic status of the cells reflected in the highly variable cellular acetyl phosphate concentration.

GlgS is a 7892-Da protein which is involved in glycogen biosynthesis in bacteria. We report the 1H, 15N and 13C NMR assignments of the backbone and side-chain resonances at 25 degrees C and pH 6.7 from two-dimensional homonuclear and three-dimensional heteronuclear NMR experiments. The secondary structure of the protein was determined using sequential and medium-range NOE correlations, vicinal 3J(NH-H alpha) coupling values and amide proton exchange rates. The secondary structure obtained is consistent with the secondary chemical shifts of 1H alpha, 13C alpha and 13C = O. It was found that the secondary structure of GlgS comprises two amphipathic helices (Asn10-Met21 and Glu39-Arg60), one short highly hydrophobic helix (Ile30-Val33), a short extended beta-strand-like fragment (Arg26-Asp29) and two type I beta-turns (His22-Gly25 and Thr34-Met37). An overall topology of GlgS is suggested based on long-range NOEs. The elements of secondary structure form a sandwich in which the beta-strand and the short hydrophobic helix are positioned between the two amphipathic helices.

The hfq-encoded RNA-binding protein HF-I has long been known as a host factor for phage Qbeta RNA replication and has recently been shown to be essential for translation of rpoS, which encodes the sigmaS subunit of RNA polymerase. Here we demonstrate that an hfq null mutant does not synthesize glycogen, is starvation and multiple stress sensitive, and exhibits strongly reduced expression of representative sigmaS-regulated genes. These phenotypes are consistent with strongly reduced sigmaS levels in the hfq mutant. However, the analysis of global protein synthesis patterns on two-dimensional O'Farrell gels indicates that approximately 40% of the more than 30 proteins whose syntheses are altered in the hfq null mutant are not affected by an rpoS mutation. We conclude that HF-I is a global regulator involved in the regulation of expression of sigmaS and sigmaS-independent genes.

The rpoS-encoded sigma(S) subunit of RNA polymerase is a central regulator in a regulatory network that governs the expression of many stationary phase-induced and osmotically regulated genes in Escherichia coli. sigma(S) is itself induced under these conditions due to an increase in rpoS transcription (only in rich media) and rpoS translation as well as a stabilization of sigma(S) protein which in growing cells is subject to rapid turnover. We demonstrate here that a response regulator, RssB, plays a crucial role in the control of the cellular sigma(S) content. rssB null mutants exhibit nearly constitutively high levels of sigma(S) and are impaired in the post-transcriptional growth phase-related and osmotic regulation of sigma(S). Whereas rpoS translational control is not affected, sigma(S) is stable in rssB mutants, indicating that RssB is essential for sigma(S) turnover. RssB contains a unique C-terminal output domain and is the first known response regulator involved in the control of protein turnover.