Sierra platinum: a fast and robust peak-caller for replicated ChIP-seq experiments with visual quality-control and -steering

Background: Histone modifications play an important role in gene regulation. Their genomic locations are of great interest. Usually, the location is measured by ChIP-seq and analyzed with a peak-caller. Replicated ChIP-seq experiments become more and more available. However, their analysis is based on single-experiment peak-calling or on tools like PePr which allows peak-calling of replicates but whose underlying model might not be suitable for the conditions under which the experiments are performed. Results: We propose a new peak-caller called \"Sierra Platinum\" that allows peak-calling of replicated ChIP-seq experiments. Moreover, it provides a variety of quality measures together with integrated visualizations supporting the assessment of the replicates and the resulting peaks, as well as steering the peak-calling process. Conclusion: We show that Sierra Platinum outperforms currently available methods using a newly generated benchmark data set and using real data from the NIH Roadmap Epigenomics Project. It is robust against noisy replicates

Linking active margin dynamics to overriding plate deformation: Synthesizing geophysical images with geological data from the Norfolk Basin

The Tonga-Kermadec subduction system in the southwest Pacific preserves a series of crustal elements and sediments which have recorded subduction initiation, rift, and back-arc basin formation. The Norfolk Basin is the farthest landward of all back-arc basins formed in the Tonga-Kermadec region and may preserve the earliest record of subduction initiation regionally. For the Norfolk Basin, we use a set of multibeam bathymetry, magnetic, and seismic reflection and refraction data to constrain basin structure and the mode and timing of formation. A structural interpretation reveals a two-stage tectonic evolution: (1) a convergent tectonic regime until 38–34 Ma, alternatively related to island arc collision or subduction initiation, and (2) lithospheric extension after 34 Ma. These observations may help to constrain mechanical models that predict rapid extension following convergence of the overriding plate during subduction initiation or arc reversals

Comparison of different CT metal artifact reduction strategies for standard titanium and carbon-fiber reinforced polymer implants in sheep cadavers

BACKGROUND CT artifacts induced by orthopedic implants can limit image quality and diagnostic yield. As a number of different strategies to reduce artifact extent exist, the aim of this study was to systematically compare ex vivo the impact of different CT metal artifact reduction (MAR) strategies on spine implants made of either standard titanium or carbon-fiber-reinforced-polyetheretherketone (CFR-PEEK). METHODS Spine surgeons fluoroscopically-guided prepared six sheep spine cadavers with pedicle screws and rods of either titanium or CFR-PEEK. Samples were subjected to single- and dual-energy (DE) CT-imaging. Different tube voltages (80, DE mixed, 120 and tin-filtered 150 kVp) at comparable radiation dose and iterative reconstruction versus monoenergetic extrapolation (ME) techniques were compared. Also, the influence of image reconstruction kernels (soft vs. bone tissue) was investigated. Qualitative (Likert scores) and quantitative parameters (attenuation changes induced by implant artifact, implant diameter and image noise) were evaluated by two independent radiologists. Artifact degree of different MAR-strategies and implant materials were compared by multiple ANOVA analysis. RESULTS CFR-PEEK implants induced markedly less artifacts than standard titanium implants (p < .001). This effect was substantially larger than any other tested MAR technique. Reconstruction algorithms had small impact in CFR-PEEK implants and differed significantly in MAR efficiency (p < .001) with best MAR performance for DECT ME 130 keV (bone kernel). Significant differences in image noise between reconstruction kernels were seen (p < .001) with minor impact on artifact degree. CONCLUSIONS CFR-PEEK spine implants induce significantly less artifacts than standard titanium compositions with higher MAR efficiency than any alternate scanning or image reconstruction strategy. DECT ME 130 keV image reconstructions showed least metal artifacts. Reconstruction kernels primarily modulate image noise with minor impact on artifact degree

Long-wavelength tilting of the Australian continent since the Late Cretaceous

Global sea level and the pattern of marine inundation on the Australian continent are inconsistent. We quantify this inconsistency and show that it is partly due to a long wavelength, anomalous, downward tilting of the continent to the northeast by 300 m since the Eocene. This downward tilting occurred as Australia approached the subduction systems in South East Asia and is recorded by the progressive inundation of the northern margin of Australia. From the Oligocene to the Pliocene, the long wavelength trend of anomalous topography shows that the southern margin of Australia is characterized by relative subsidence. We quantify the anomalous topography of the Australian continent by computing the displacement needed to reconcile the interpreted pattern of marine incursion with a predicted topography in the presence of global sea level variations. On the southern margin, long wavelength subsidence was augmented by at least 250 m of shorter wavelength anomalous subsidence, consistent with the passage of the southern continental margin over a north–south elongated, 500 km wide, topographic anomaly approximately fixed with respect to the mantle. The present day reconstructed position of this depth anomaly is aligned with the Australian Antarctic Discordance and is consistent with the predicted passage of the Australian continent over a previously subducted slab. Both the long-wavelength continental tilting and smaller-scale paleo-topographic anomaly on the southern Australian margin may have been caused by subduction-generated dynamic topography. These new constraints on continental vertical motion are consistent with the hypothesis that mantle convection induced topography is of the same order of magnitude as global sea level change

Methodische Untersuchungen zur Variation der Mengen- und Spurenelementkonzentrationen in Pferdekotproben im Tagesverlauf und über einen 15-Tages-Zeitraum

Um Kotproben für die Beurteilung der Mineralstoffversorgung von Pferden nutzen zu können, bedarf es methodischer Untersuchungen zur Standardisierung der Probenentnahme. Untersucht wurden der Einfluss des Entnahmezeitpunktes sowie die Konzentrationsentwicklung von 28 Mengen- und Spurenelementen über einen 15-Tages-Zeitraum. Als Probanden standen sechs Pferde zur Verfügung, die in drei Fütterungsgruppen eingeteilt waren und Rationen mit unterschiedlichen Mineralstoffkonzentrationen (ohne Ergänzung, mit definierter Zulage und mit freiem Zugang zu einer Mineralleckmasse) erhalten haben. Die Kotproben wurden über 15 Tage an jedem dritten Tag um 7 Uhr und an Tag 6 alle sechs Stunden aus der Ampulla recti gewonnen. Die Analyse der 28 ausgewählten Elemente in den zuvor getrockneten Kotproben erfolgte mithilfe von optischer Emissionsspektrometrie mittels induktiv gekoppelten Plasmas (ICP-OES) bzw. durch Massenspektrometrie mit induktiv gekoppeltem Plasma (ICP-MS). Zur statistischen Auswertung wurde das Verfahren des linearen gemischten Modells einer Varianzanalyse mit festen Effekten (Tiernummer und Entnahmezeitpunkt bzw. Tag) gewählt, nach dem die Residuen mithilfe des Shapiro-Wilk-Testes auf Normalverteilung geprüft wurden. Bei signifikanten Unterschieden (p < 0,05) schloss sich ein Post-hoc-Test mit Bonferroni-Korrektur an. Die Konzentration der im Kot gemessenen Mengen- und Spurenelemente, die zu unterschiedlichen Uhrzeiten genommenen wurden, unterscheidet sich lediglich im Fall von Kalium signifikant. Die Variabilität der Messwerte ist jedoch so gering, dass die Autoren von keinem für die praktische Anwendung bedeutendem Einfluss des Entnahmezeitpunktes ausgehen. Bei einer konstanten Fütterung hat der Zeitpunkt der Probennahme keinen Einfluss auf das Ergebnis. Die Messwerte der 15-Tage-Verlaufstudie präsentierten sich für den Großteil der gemessenen Elemente innerhalb der jeweiligen Fütterungsgruppe gleichbleibend, weshalb davon ausgegangen werden kann, dass bei gleichbleibender Fütterung die Ausscheidung mit dem Kot konstant ist

Keratinocyte growth factor, tumor necrosis factor-alpha and interleukin-1 beta gene expression in cultured fibroblasts and keratinocytes from burned patients

PURPOSE: To evaluate the gene expression of KGF, TNF-alpha and IL-1 beta in skin fibroblasts and keratinocytes cultured from burned patients. METHODS: Three patients with large burns and three patients with small burns, as well as two controls, were included. The cell culture was initiated by the enzymatic method. After extraction and purification of mRNA, qPCR was used to assess the gene expression of KGF, TNF-alpha and IL-1 beta. RESULTS: The expression of KGF was increased on average 220-fold in large burns and 33.33-fold in small burns in fibroblasts, and 11.2-fold in large burns and 3.45-fold in small burns in keratinocytes compared to healthy patients (p<0.05). Expression of TNF-alpha was not observed. IL-1 beta is down-regulated in fibroblasts of burned patients, and much more repressed in small burns (687-fold, p<0.05). In keratinocytes, the repression of IL-1 beta expression occurs in patients with small burns (28-fold), while patients with large burns express this gene intensively (15-fold). CONCLUSIONS: The study showed a quantitative pattern in the expression of KGF gene, which is more expressed according to the size of the burn. TNF-alpha was not expressed. A qualitative pattern in the expression of IL-1 beta gene was demonstrated.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)UNIFESP-EPM Department of SurgeryUNIFESP-EPMUNIFESP-EPM Department of GynecologyUNIFESP, EPM, Department of SurgeryUNIFESP-EPMUNIFESP, EPM Department of GynecologySciEL

Sex differences in the functional connectivity of the amygdalae in association with cortisol

Human amygdalae are involved in various behavioral functions such as affective and stress processing. For these behavioral functions, as well as for psychophysiological arousal including cortisol release, sex differences are reported.Here, we assessed cortisol levels and resting-state functional connectivity (rsFC) of left and right amygdalae in 81 healthy participants (42 women) to investigate potential modulation of amygdala rsFC by sex and cortisol concentration.Our analyses revealed that rsFC of the left amygdala significantly differed between women and men: Women showed stronger rsFC than men between the left amygdala and left middle temporal gyrus, inferior frontal gyrus, postcentral gyrus and hippocampus, regions involved in face processing, inner-speech, fear and pain processing. No stronger connections were detected for men and no sex difference emerged for right amygdala rsFC. Also, an interaction of sex and cortisol appeared: In women, cortisol was negatively associated with rsFC of the amygdalae with striatal regions, mid-orbital frontal gyrus, anterior cingulate gyrus, middle and superior frontal gyri, supplementary motor area and the parietal–occipital sulcus. Contrarily in men, positive associations of cortisol with rsFC of the left amygdala and these structures were observed. Functional decoding analyses revealed an association of the amygdalae and these regions with emotion, reward and memory processing, as well as action execution.Our results suggest that functional connectivity of the amygdalae as well as the regulatory effect of cortisol on brain networks differs between women and men. These sex-differences and the mediating and sex-dependent effect of cortisol on brain communication systems should be taken into account in affective and stress-related neuroimaging research. Thus, more studies including both sexes are required

TRASTORNOS DEL APRENDIZAJE: INVESTIGACIONES PSICOLÓGICAS Y PSICOPEDAGÓGICAS EN DIVERSOS PAÍSES DE SUD AMÉRICA

The present study addresses a review on the origin of research and work strategies implemen- ted on children with Learning Difficulties in several South American countries. Initially, it describes the clinical neurological and psychological investigations, outlining afterwards researches and psychopeda- gogic strategies conducted at schools. The aim is to bring to light a historical perspective of the different strategies that have been developed in each of the studied countries.El presente artículo hace una reseña del origen de las investigaciones y estrategias de trabajo con niños que presentan Dificultades de Aprendizaje en varios países de Sud América. Aborda inicialmente las investigaciones clínicas neurológicas y psicológicas y luego los estudios y estrategias psicopedagógicas para el trabajo en las escuelas. Su objetivo es mostrar una visión histórica de las dis- tintas estrategias que ha elaborado cada uno de los países estudiados

Standardization of Marine Meteorological Data from FINO Offshore Platforms

KlimawandelDer Ausbau der Offshore-Windenergie gehört zu den erklärten Zielen der Bundesregierung. Um bessere Ken ntnisse der Bedingungen auf See zu erlangen, wurden drei Forschungsplattformen in der Nordsee (FINO 1 und 3) und Ostsee (FINO 2) errichtet. An diesen werden meteorologische und ozeanographische Größen in unterschiedlichen Höhen gemessen, um unter anderem Aussagen zu Vertikalprofilen der Windgeschwindigkeit treffen zu können. Da sich die Plattformen und Masten im Design unterscheiden und sich insbesondere bei den Windmessungen deutlich ein richtungsabhängiger Einfluss auf die Messungen zeigt, ist für die Vergleichbarkeit der Standorte eine standardisierte Auswertung der Messergebnisse erforderlich. Ziel des Projektes FINO-Wind ist es, die Vergleichbarkeit der Daten der drei Standorte zu verbessern und den Datennutzern nach standardisierten Methoden qualitätsgeprüfte Daten zur Verfügung zu stellen. Es sollen deshalb Standardisierungsverfahren zur Auswertung der Winddaten entwickelt werden. Insbesondere die verschiedenen Masteffekte werden eingehend untersucht und durch Windkanalmessungen, Vergleich mit LiDAR-Daten, CFD (Computational Fluid Dynamics)-Modellierungen und Anwendung der UAM (Uniform ambient flow mast correction)-Methode abgeschätzt. Daraus werden Korrekturfaktoren für Windmessungen abgeleitet, die später angewendet werden sollen. Die Messdaten, die als 10-Minuten-Werte vorliegen, werden des Weiteren einer umfassenden und automatisierten Qualitätsprüfung unterzogen. Dabei durchlaufen die Daten in aufeinanderfolgenden Schritten formale, klimatologische, zeitliche, Wiederholungs- und Konsistenzprüfungen und werden nach erfolgreichem Abschluss jeder Sequenz mit spezifischen Qualitätsflags gekennzeichnet. Aus der Analyse und dem Vergleich der Instrumentierung in unterschiedlichen Höhen, der Installation und Ausrichtung sowie die Mastkonstruktionen sollen Empfehlungen herausgearbeitet werden, wie zukünftige Anwendungen im Bereich der Offshore-Windmessungen verbessert werden können