66 research outputs found
Chemical weathering and provenance evolution of Holocene–Recent sediments from the Western Indus Shelf, Northern Arabian Sea inferred from physical and mineralogical properties
We present a multi-proxy mineral record based on X-ray diffraction and diffuse reflectance spectrophotometry analysis for two cores from the western Indus Shelf in order to reconstruct changing weathering intensities, sediment transport, and provenance variations since 13 ka. Core Indus-10 is located northwest of the Indus Canyon and exhibits fluctuations in smectite/(illite + chlorite) ratios that correlate with monsoon intensity. Higher smectite/(illite + chlorite) and lower illite crystallinity, normally associated with stronger weathering, peaked during the Early–Mid Holocene, the period of maximum summer monsoon. Hematite/goethite and magnetic susceptibility do not show clear co-variation, although they both increase at Indus-10 after 10 ka, as the monsoon weakened. At Indus-23, located on a clinoform just west of the canyon, hematite/goethite increased during a period of monsoon strengthening from 10 to 8 ka, consistent with increased seasonality and/or reworking of sediment deposited prior to or during the glacial maximum. After 2 ka terrigenous sediment accumulation rates in both cores increased together with redness and hematite/goethite, which we attribute to widespread cultivation of the floodplain triggering reworking, especially after 200 years ago. Over Holocene timescales sediment composition and mineralogy in two localities on the high-energy shelf were controlled by varying degrees of reworking, as well as climatically modulated chemical weathering
Impairment of trophic interactions between zebrafish ( Danio rerio ) and midge larvae ( Chironomus riparius ) by chlorpyrifos
The effects of chemicals on biotic interactions, such as competition and predation, have rarely been investigated in aquatic ecotoxicology. This study presents a new approach for the investigation of predator-prey interactions between zebrafish (Danio rerio) and midge larvae (Chironomus riparius) impaired by chlorpyrifos (CHP), a neurotoxic insecticide. With a simple experimental design including four different treatments: (1) control, (2) predator exposed, (3) prey exposed and (4) both, predator and prey, exposed, we were able to detect by visual observation an increase in the feeding rate of zebrafish preying on exposed chironomids after acute (2h) exposure to 6μg/l CHP. Previously, a decrease in the burrowing behaviour of exposed chironomid larvae was observed. However, when pre-exposing simultaneously both predators and prey, no significant differences in the feeding rate of zebrafish were observed. This suggests an impairment in prey recognition of the exposed zebrafish. At a lower CHP concentration (1μg/l), no differences in feeding rate of zebrafish were observed. We therefore propose the use of trophic interactions as parameters in higher tier studies for chemical testing and evaluation of ecotoxicological risk assessmen
Patterns of biomedical science production in a sub-Saharan research center
<p>Abstract</p> <p>Background</p> <p>Research activities in sub-Saharan Africa may be limited to delegated tasks due to the strong control from Western collaborators, which could lead to scientific production of little value in terms of its impact on social and economic innovation in less developed areas. However, the current contexts of international biomedical research including the development of public-private partnerships and research institutions in Africa suggest that scientific activities are growing in sub-Saharan Africa. This study aims to describe the patterns of clinical research activities at a sub-Saharan biomedical research center.</p> <p>Methods</p> <p>In-depth interviews were conducted with a core group of researchers at the Medical Research Unit of the Albert Schweitzer Hospital from June 2009 to February 2010 in Lambaréné, Gabon. Scientific activities running at the MRU as well as the implementation of ethical and regulatory standards were covered by the interview sessions.</p> <p>Results</p> <p>The framework of clinical research includes transnational studies and research initiated locally. In transnational collaborations, a sub-Saharan research institution may be limited to producing confirmatory and late-stage data with little impact on economic and social innovation. However, ethical and regulatory guidelines are being implemented taking into consideration the local contexts. Similarly, the scientific content of studies designed by researchers at the MRU, if local needs are taken into account, may potentially contribute to a scientific production with long-term value on social and economic innovation in sub-Saharan Africa.</p> <p>Conclusion</p> <p>Further research questions and methods in social sciences should comprehensively address the construction of scientific content with the social, economic and cultural contexts surrounding research activities.</p
Distinct patterns of functional and effective connectivity between perirhinal cortex and other cortical regions in recognition memory and perceptual discrimination.
Traditionally, the medial temporal lobe (MTL) is thought to be dedicated to declarative memory. Recent evidence challenges this view, suggesting that perirhinal cortex (PrC), which interfaces the MTL with the ventral visual pathway, supports highly integrated object representations in recognition memory and perceptual discrimination. Even with comparable representational demands, perceptual and memory tasks differ in numerous task demands and the subjective experience they evoke. Here, we tested whether such differences are reflected in distinct patterns of connectivity between PrC and other cortical regions, including differential involvement of prefrontal control processes. We examined functional magnetic resonance imaging data for closely matched perceptual and recognition memory tasks for faces that engaged right PrC equivalently. Multivariate seed analyses revealed distinct patterns of interactions: Right ventrolateral prefrontal and posterior cingulate cortices exhibited stronger functional connectivity with PrC in recognition memory; fusiform regions were part of the pattern that displayed stronger functional connectivity with PrC in perceptual discrimination. Structural equation modeling revealed distinct patterns of effective connectivity that allowed us to constrain interpretation of these findings. Overall, they demonstrate that, even when MTL structures show similar involvement in recognition memory and perceptual discrimination, differential neural mechanisms are reflected in the interplay between the MTL and other cortical regions
Nachnutzung der gemeinsamen JOIN –Repository-Infrastruktur für den KDSF-Objektbereich Publikation?
Im Rahmen des JOIN2-Projekts haben Bibliotheks- & Dokumentationseinheiten (Deutsches Elektronensynchrotron DESY Hamburg/Zeuten, Deutsches Krebsforschungszentrum DKFZ Heidelberg, Forschungszentrum Jülich, GSI Helmholtzzentrum für Schwerionenforschung Darmstadt, Maier-Leibnitz-Zentrum Garching, Rheinisch-Westfälische Technische Hochschule (RWTH) Aachen, KIT Institut für experimentelle Kernphysik Karlsruhe) eine gemeinsame Repository-Infrastruktur für ihre Wissenschaftler und Wissenschaftlerinnen geschaffen. Das Poster dokumentiert Überlegungen, welche Anforderungen des Kerndatensatzes Forschung im Objektbereich abgebildet werden können, wo Probleme und fehlende Normierungen in der Praxis auftauchen könnten und vor allem, an welchen Stellen Kompromisse in Hinblick auf die JOIN2-Serviceorientierung für den Wissenschaftsbereich eingegangen werden müssen.Schlagwörter: Repositorium; VeröffentlichungsdatenbankSchwerpunktbereich: Identifikatoren & Anbindung von Drittsystemen, z.B. von Repositorie
Constructive approach to limiting periodic orbits with exponential and power law dynamics
In dynamical systems limit cycles arise as a result of a Hopf bifurcation,
after a control parameter has crossed its critical value. In this study we
present a constructive method to produce dissipative dynamics which lead to
stable periodic orbits as time grows, with predesigned transient dynamics.
Depending on the construction method a) the limiting orbit can be a regular
circle, an ellipse or a more complex closed orbit and b) the approach to the
limiting orbit can follow an exponential law or a power law. This technique
allows to design nonlinear models of dynamical systems with desired
(exponential or power law) relaxation properties.Comment: 17 pages, 6 figure
Expertenempfehlung: Therapie nichtgehfähiger Patienten mit Muskeldystrophie Duchenne
BACKGROUND Duchenne muscular dystrophy (DMD) is the most frequent genetic neuromuscular disease in childhood with loss of ambulation usually occurring around the age of 9-11 years.
OBJECTIVE, MATERIAL AND METHODS Based on current guidelines and clinical trials, neuropediatric and neurological experts developed recommendations for the treatment of nonambulatory DMD patients focusing on drug treatment of adults. This advisory board was sponsored by PTC Therapeutics, the distributers of the substance ataluren.
RESULTS AND CONCLUSION Loss of ambulation is heterogeneously defined across clinical trials. Among others, the need of a wheelchair, ambulation without mobility aids or maximum walking distance can be suitable parameters for assessment. Treatment of DMD patients at any stage of the disease is based on supportive and symptomatic measures, which should be continued after loss of ambulation. In addition, disease-modifying drugs are available for the treatment of DMD and glucocorticoids are the usual standard of care treatment even beyond the loss of ambulation. Ataluren, a potentially dystrophin restorative, disease-modifying treatment, has been approved for patients with DMD due to a nonsense mutation (nmDMD), which applies to approximately 13% of DMD patients and is usually combined with steroids. Clinical data from the
STRIDE registry demonstrated a delayed disease progression even after loss of ambulation. Currently, no reliable data are available for exon skipping approaches in adult DMD patients. The antioxidant idebenone could be an option in nonambulant adolescent patients not treated with glucocorticoids and without other therapeutic options. A combination treatment of idebenone and glucocorticoids is currently being investigated in a clinical trial. Add-on treatment with idebenone in addition to ataluren may be considered for nonambulant nmDMD patients. Some of the discussed treatment options are still in clinical trials or there are not enough data for older DMD patients; therefore, these expert recommendations correspond to evidence class IV.ZUSAMMENFASSUNG HINTERGRUND: Die Muskeldystrophie Duchenne (DMD) ist die häufigste genetische neuromuskuläre Krankheit im Kindesalter, bei der es meist im Alter von 9 bis 11 Jahren zum Verlust der Gehfähigkeit kommt.
ZIEL DER ARBEIT UND MATERIAL UND METHODEN Auf der Grundlage aktueller Leitlinien und Studien erarbeiteten neuropädiatrische und neurologische Experten im Rahmen eines von der Firma PTC Therapeutics GmbH (Frankfurt am Main, Deutschland), die die Substanz Ataluren vertreibt, gesponserten Advisory Boards Empfehlungen zur Behandlung nichtgehfähiger Patienten mit DMD mit Schwerpunkt medikamentöse Therapien von Erwachsenen. ERGEBNISSE UND DISKUSSION Der Verlust der Gehfähigkeit wird in Studien sehr unterschiedlich definiert und bezieht sich u. a. auf die Rollstuhlpflicht, das selbständige Gehen ohne Hilfsmittel oder die maximale Gehstrecke. Grundlage der Therapie von Patienten mit DMD in jedem Krankheitsstadium sind supportive und symptomatische Maßnahmen, die in der Regel auch nach dem Verlust der Gehfähigkeit intensiv weitergeführt werden sollten. Zusätzlich stehen den Patienten medikamentöse Therapien mit dem Ziel der Modifikation des Krankheitsverlaufes zur Verfügung. Glukokortikoide bilden den Stützpfeiler der medikamentösen Therapie auch über den Verlust der Gehfähigkeit hinaus, dann meist in reduzierter Dosis. Für Patienten mit DMD aufgrund einer Nonsense-Mutation (nmDMD), ca. 13 % aller DMD-Patienten, steht Ataluren als potenziell dystrophinwiederherstellende, krankheitsmodifizierende Therapie zur Verfügung; klinische Daten aus dem STRIDE-Register zeigen eine verzögerte Krankheitsprogression auch nach Verlust der Gehfähigkeit. Zum Exon-Skipping liegen für erwachsene Patienten derzeit noch keine belastbaren Daten vor. Das Antioxidans Idebenon kommt bei nichtgehfähigen, jugendlichen Patienten ohne therapeutische Alternative, die nicht mit Glukokortikoiden behandelt werden können, infrage. Ataluren eignet sich zur kombinierten Behandlung mit Glukokortikoiden, eine Kombination von Idebenon und Glukokortikoiden wird derzeit in einer klinischen Studie überprüft. Eine Add-on-Therapie mit Idebenon zusätzlich zu Ataluren ist bei nichtgehfähigen nmDMD-Patienten zu erwägen. Bedingt durch die Tatsache, dass sich einige der diskutierten Therapieoptionen noch in der Phase der klinischen Prüfung befinden oder noch keine oder nur begrenzte Daten für ältere Patienten mit DMD vorliegen, handelt es sich um Expertenempfehlungen entsprechend der Evidenzklasse IV
Integrated toxicity evaluation of a pulp deposit using organisms of different trophic levels
Purpose: In order to assess possible adverse effects originating from pulp deposits in a Swiss lake, a sediment quality triad approach was applied with chemical, ecotoxicological and ecological assessment methods. Materials and methods: To obtain an integrative picture of the potential ecotoxicological effects on organisms of different trophic levels, four test procedures were applied. The acute effects of pulp deposit pore water on a decomposer, the amphipod Gammarus fossarum, were monitored. Chronic toxicity of the pore water was evaluated on primary producers via a growth inhibition test with unicellular green algae (Pseudokirchneriella subcapitata) and on secondary consumers in a reproduction test with the water flea Ceriodaphnia dubia. To evaluate the effects of the pulp deposit on sediment inhabitants, a whole-life-cycle test with the non-biting midge Chironomus riparius was undertaken. Chemical assessment included dissolved organic carbon, extractable organic halogenic compounds, polychlorinated biphenyls (PCBs), polycyclic aromatic hydrocarbons (PAHs) and heavy metals. The composition of the macrozoobenthos community was analysed in order to assess the ecological effects. Results and discussion: G. fossarum displayed increased locomotor activity at 12.5% but not at 25% sample concentration during a short-time exposure of 20h. Chronic effects compromised the reproduction and growth of C. dubia (lowest observed effect concentration, 12.5% sample concentration) with zero population growth in 100% pulp deposit pore water. In 100% pulp deposit, C. riparius exhibited increased mortality at 10 and 17days after oviposition. Pulp deposits of 50% and 100% concentration caused a significantly lower emergence compared with the reference treatments (lake sediment and quartz sand). Additionally, the locomotor activity of chironomids decreased significantly in 25-100% pulp deposit. No chronic effects of pulp deposit pore water on algae photosynthesis and growth could be detected. The bioassay results were in accordance with an elevated content of PAHs, PCBs and metals in the pulp deposit. Significantly more organisms known to be tolerant to organic pollution were present within the macrozoobenthos community. Conclusions: In general, for sediment inhabitants such as chironomids, the pulp deposit has to be classified toxic. In the present test setup, the toxicity of the pulp deposit was reflected better by the chronic test systems applied than by the acute ones. The applied testing framework could be a suitable tool to assess the risk of contaminated sites, and this information will help decide whether risk mitigation measures should be taken. In addition, with a similar approach, the success of any mitigation measures taken can be assesse
KoKoN – Ein Expertenwalkthrough zu digitalen Lehr-Kooperationen im Kontext der Nationalen Bildungsplattform
... Für die erfolgreiche Umsetzung digitalgestützter Lehre nehmen sowohl hochschulinterne als auch -übergreifende Kooperationen einen immer höheren ... Stellenwert ein. Die damit einhergehende Vernetzung und das Zusammenwirken verschiedener Bildungsanbieter bilden die Grundlage des lebenslangen Lernens sowie der bildungsbereichübergreifenden Gestaltung von individuellen Bildungsbiografien (vgl. Schleifenbaum, & Walther, 2015). Die Anbahnung und Durchführung von insbesondere digitalen Lehr-Kooperationen erfordern über reine IT-Kenntnisse hinausgehende Kompetenzen seitens der Lehrenden. Für gelingende Kooperationsprozesse zwischen Lehrenden sind daher weitere Facetten digitaler Kompetenz erforderlich, wie bspw. bzgl. der Durchführung von Kommunikationsund Kooperationsprozessen im digitalen Raum, des Aufbaus einer eigenen digitalen Lehr- und Forscher:innen-Identität sowie der Reflexion des eigenen digitalen Lehr-Handelns (Eichhorn, Müller, & Tillmann, 2017; Eichhorn, 2020). [Aus: Herausforderungen für die digitalgestützte Hochschullehre
Pediatric T-ALL type-1 and type-2 relapses develop along distinct pathways of clonal evolution
The mechanisms underlying T-ALL relapse remain essentially unknown. Multilevel-omics in 38 matched pairs of initial and relapsed T-ALL revealed 18 (47%) type-1 (defined by being derived from the major ancestral clone) and 20 (53%) type-2 relapses (derived from a minor ancestral clone). In both types of relapse, we observed known and novel drivers of multidrug resistance including MDR1 and MVP, NT5C2 and JAK-STAT activators. Patients with type-1 relapses were specifically characterized by IL7R upregulation. In remarkable contrast, type-2 relapses demonstrated (1) enrichment of constitutional cancer predisposition gene mutations, (2) divergent genetic and epigenetic remodeling, and (3) enrichment of somatic hypermutator phenotypes, related to BLM, BUB1B/PMS2 and TP53 mutations. T-ALLs that later progressed to type-2 relapses exhibited a complex subclonal architecture, unexpectedly, already at the time of initial diagnosis. Deconvolution analysis of ATAC-Seq profiles showed that T-ALLs later developing into type-1 relapses resembled a predominant immature thymic T-cell population, whereas T-ALLs developing into type-2 relapses resembled a mixture of normal T-cell precursors. In sum, our analyses revealed fundamentally different mechanisms driving either type-1 or type-2 T-ALL relapse and indicate that differential capacities of disease evolution are already inherent to the molecular setup of the initial leukemia
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