929 research outputs found

    The Impact of TGF-ß, GM-CSF and Antibody Response for Diagnosis as well as Etiopathology of Lyme Disease

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    In this study the pathogenesis of lyme disease was investigated in vivo by means of the wild-type mouse strains C3H/HeN and FVB/N as well as transgenic mouse strains, which are tissue specific modulated in their TGF-ß or GM-CSF (granulocyte-monocyte colony stimulating factor) activity and sensitivity. The mice were infected intradermally with B. burgdorferi. Progression of lyme disease was monitored using a number of diagnostic tests (recultivation of borrelia from tissue, ELISA, Western blot, histologic analysis). The study confirms the mouse strain FVB/N WT (wild type) to be susceptible to B. burgdorferi infections and that this represents a suitable in vivo model for investigations concerning the progression of a B. burgdorferi infection. We further demonstrate transgenic modification of TGF-ß or GM-CSF activity, and sensitivity in T cells and epithelium respectively, do not affect the pathogenesis of lyme disease. Our data show a positive linear correlation between antibody response and the severity of arthritic processes due to B. burgdorferi infection. Determination of the increase in antibody titer in sera of infected organisms therefore might be a useful tool to predict the progression of inflammatory processes in the course of lyme disease

    On the fluid-mobility of molybdenum, tungsten, and antimony in subduction systems

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    Molybdenum (Mo) and tungsten (W) have long been regarded as being more or less immobile during slab fluid-induced arc magma generation. Here we characterize about 180 samples of young, predominantly mafic to intermediate tephras and lavas for their Mo, W, and antimony (Sb) concentrations, to examine the fluid-mobility of these elements in subduction systems. Samples were taken along the active arcs of the Chilean Southern Volcanic Zone (SVZ) and the Central American Volcanic Arc (CAVA). When relating Mo, W, and Sb to trace element ratios typically used to constrain the involvement of subduction fluids in magma formation, such as Ba/La or U/Th, Mo, W, and Sb are enriched in the most fluid-influenced, highest-degree melts. W/Mo ratios correlate positively with Pb/Ce, which is established to reflect a recent subduction signal or assimilation of crustal material with an ancient subduction signature, suggesting that subduction processes promote enrichment of W over Mo. This is well expressed at the SVZ and most of the CAVA; while few OIB-type rocks from Central Costa Rica form an opposite trend. Moreover, Mo/W ratios co-vary with Cl contents derived from melt inclusions, indicating that the relative degree of mobilization responds to the composition of the subduction fluid. To evaluate the mobility of Mo, W, and Sb during metamorphism in the slab, eclogites with no or minor metasomatic overprint and a fluid-induced overprint in an eclogite-blueschist sequence were investigated. None of the three elements shows a systematic variability related to metasomatism and the minor variations are interpreted to reflect protolith heterogeneity. This suggests that Mo, W and Sb remain relatively immobile up to depths of 70 km in the subduction zone

    Afterpulse Measurements of R7081 Photomultipliers for the Double Chooz Experiment

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    We present the results of afterpulse measurements performed as qualification test for 473 inner detector photomultipliers of the Double Chooz experiment. The measurements include the determination of a total afterpulse occurrence probability as well as an average time distribution of these pulses. Additionally, more detailed measurements with different light sources and simultaneous charge and timing measurements were performed with a few photomultipliers to allow a more detailed understanding of the effect. The results of all measurements are presented and discussed

    Leistungserwartungen und neuropsychologische Defizite bei Menschen mit depressiven Störungen - Ein experimentelles Design zur Untersuchung des Zusammenhangs von induzierten Leistungserwartungen und der Leistungsperformanz in der neuropsychologischen Facette des verbalen Gedächtnisses

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    Hintergrund: Dysfunktionale Erwartungen können als Kernsymptom depressiver Störungen verstanden werden. Erkenntnisse aus der Verhaltenspsychologie legen nahe, dass Erwartungen grundsätzlich durch Interventionen modifizierbar sind und kognitive sowie motorische Leistungen darüber beeinflusst werden können. Beobachtbare Placeboeffekte und vielversprechende Ergebnisse aus der Therapieforschung für Angsterkrankungen machen Hoffnung darauf, dass Erwartungseffekte auch in der Therapie von Depressionen, beispielsweise als Erwartungsfokussierte Psychotherapeutische Interventionen (EFPI), eine Rolle spielen könnten. Bisher wurde allerdings noch nicht untersucht, ob Erwartungseffekte auch einen Einfluss auf die Leistungsfähigkeiten in defizitären neuropsychologischen Bereichen wie dem verbalen Gedächtnis haben können. Zielsetzung: Ziel dieser Studie war es daher, zum einen die Beeinflussbarkeit der aufgabenspezifischen Leistungserwartung durch positives Feedback zu untersuchen und zum anderen den Zusammenhang zwischen positivem Feedback und der Leistung im verbalen Kurzzeit- und Arbeitsgedächtnis bzw. zwischen der Leistungserwartung und der Testleistung zu analysieren. Methodik: Zu diesem Zweck wurde auf Grundlage einer Vorstudie ein Online-Experiment entwickelt, in dem die verbale Gedächtnisleistung und die situationsspezifischen Leistungserwartungen bei depressiven Personen (n = 76) untersucht wurden. Zunächst wurde die aufgabenspezifische Leistungserwartung erhoben und eine erste Version des verbalen Lern- und Merkfähigkeitstests bearbeitet. Anschließend wurde der Experimentalgruppe (n = 39) ein standardisiert positives Leistungsfeedback präsentiert, während die Kontrollgruppe (n = 37) einen neutralen Informationstext erhielt. Daraufhin wurde erneut die aufgabenspezifische Leistungserwartung abgefragt und eine zweite Version des verbalen Lern- und Merkfähigkeitstests absolviert. Die Entwicklung der Leistungserwartung zwischen den beiden Testdurchläufen, die Entwicklung der Testleistung im verbalen Kurzzeit- und Arbeitsgedächtnis und der Zusammenhang der beiden Aspekte wurden in den jeweiligen Gruppen analysiert und verglichen. Ergebnisse: Die statistischen Analysen zeigten, dass die Leistungserwartung, wie vorhergesagt, in der Experimentalgruppe (positives Feedback) zwischen den beiden Erhebungszeitpunkten signifikant mehr zunahm als in der Kontrollgruppe (neutrales Feedback), sodass von einer positiven Beeinflussbarkeit der aufgabenspezifischen Leistungserwartung durch positives Feedback auszugehen war. Hingegen ließ sich in der Experimentalgruppe im Vergleich zur Kontrollgruppe keine signifikant größere Leistungsverbesserung im verbalen Kurzzeit- und Arbeitsgedächtnis zwischen den beiden Testdurchläufen feststellen, was nicht dem erwarteten Effekt entsprach. Außerdem zeigte sich in der Experimentalgruppe entgegen der Vermutung kein signifikant positiver Zusammenhang zwischen der Entwicklung der Leistungserwartung und der Entwicklung der Testleistung zwischen den beiden Erhebungszeitpunkten. Vielmehr deuteten die Ergebnisse auf einen signifikant negativen Zusammenhang hin. Diskussion: Die Ergebnisse der Untersuchung legen nahe, dass eine Induktion positiver Leistungserwartungen bezüglich eines neuropsychologischen Testverfahrens durch positives Feedback möglich ist. Dies steht im gewissen Widerspruch zu Forschungsarbeiten, die kognitive Immunisierungsstrategien im Rahmen von depressiven Erkrankungen als Hindernis für eine positive Erwartungsanpassung beschreiben. Methodische Unterschiede werden als Grund diskutiert; möglicherweise könnte die Stichprobencharakteristik einen entscheidenden Einfluss besitzen. Eine positive Beeinflussbarkeit der getesteten Gedächtnisleistung durch positives Feedback bzw. positive Leistungserwartungen schien jedoch nicht möglich zu sein, was ein wesentlicher Unterschied zu Gesunden sein könnte. Als mögliche Erklärung für den überraschend negativen Zusammenhang zwischen der Leistungserwartung und der Testleistung wird ein spezifisches Defizit im motivationalen bzw. volitionalen Verhalten diskutiert, das die scheinbar widersprüchliche negative Auswirkung von positivem Feedback bzw. positiven angegebenen Erwartungen auf die Testleistung aufklären könnte. Ausblick: Zukünftige Arbeiten sollten insbesondere die Zusammenhänge zwischen positivem Feedback und neuropsychologischen Testleistungen tiefergehend untersuchen. Die zusätzliche Messung von Motivation und Anstrengung könnten das bisherige experimentelle Paradigma in einem persönlichen Setting sinnvoll ergänzen. Auf klarer definierte Stichprobenkriterien, beispielsweise hinsichtlich der Akuität des Krankheitsbildes oder der Symptomschwere, sollte geachtet werden. Ein besseres Verständnis der beobachteten Zusammenhänge könnte wichtige Konsequenzen für die Weiterentwicklung psychotherapeutischer bzw. kognitionstherapeutischer Maßnahmen in der Depressionsbehandlung mit sich führen

    Longitudinal analysis of the developing rhesus monkey brain using magnetic resonance imaging: birth to adulthood.

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    We have longitudinally assessed normative brain growth patterns in naturalistically reared Macaca mulatta monkeys. Postnatal to early adulthood brain development in two cohorts of rhesus monkeys was analyzed using magnetic resonance imaging. Cohort A consisted of 24 rhesus monkeys (12 male, 12 female) and cohort B of 21 monkeys (11 male, 10 female). All subjects were scanned at 1, 4, 8, 13, 26, 39, and 52 weeks; cohort A had additional scans at 156 weeks (3 years) and 260 weeks (5 years). Age-specific segmentation templates were developed for automated volumetric analyses of the T1-weighted magnetic resonance imaging scans. Trajectories of total brain size as well as cerebral and subcortical subdivisions were evaluated over this period. Total brain volume was about 64 % of adult estimates in the 1-week-old monkey. Brain volume of the male subjects was always, on average, larger than the female subjects. While brain volume generally increased between any two imaging time points, there was a transient plateau of brain growth between 26 and 39 weeks in both cohorts of monkeys. The trajectory of enlargement differed across cortical regions with the occipital cortex demonstrating the most idiosyncratic pattern of maturation and the frontal and temporal lobes showing the greatest and most protracted growth. A variety of allometric measurements were also acquired and body weight gain was most closely associated with the rate of brain growth. These findings provide a valuable baseline for the effects of fetal and early postnatal manipulations on the pattern of abnormal brain growth related to neurodevelopmental disorders

    Towards FAIR Data in Heterogeneous Catalysis Research

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    This poster elaborates on the challenges of developing a database for heterogeneous catalysis research and FAIRmat’s effort in tayloring NOMAD schemas and search interface for catalysis researchers as well as demonstrating first steps of an ontology development for catalysis. The poster has been presented in the 1st Conference on Research Data Infrastructure (CoRDI 2023) which took place on Septmeber 12 - 14, 2023, in Karlsruhe, Germany.Funding statement: FAIRmat is a consortium of German National Research Data Infrastructure (NDFI) funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) – project 460197019

    Sepsis Diagnostics: Intensive Care Scoring Systems Superior to MicroRNA Biomarker Testing

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    Sepsis represents a serious medical problem accounting for numerous deaths of critically ill patients in intensive care units (ICUs). An early, sensitive, and specific diagnosis is considered a key element for improving the outcome of sepsis patients. In addition to classical laboratory markers, ICU scoring systems and serum miRNAs are discussed as potential sepsis biomarkers. In the present prospective observational study, the suitability of miRNAs in sepsis diagnosis was tested based on proper validated and normalized data (i.e., absolute quantification by means of Droplet Digital PCR (ddPCR)) in direct comparison to classical sepsis markers and ICU scores within the same patient cohort. Therefore, blood samples of septic intensive care patients (n = 12) taken at day of admission at ICU were compared to non-septic intensive care patients (n = 12) and a healthy control group (n = 12). Our analysis indicates that all tested biomarkers have only a moderate informative power and do not allow an unequivocal differentiation between septic and non-septic ICU patients. In conclusion, there is no standalone laboratory parameter that enables a reliable diagnosis of sepsis. miRNAs are not superior to classical parameters in this respect. It seems recommendable to measure multiple parameters and scores and to interpret them with regard to the clinical presentation

    Aerosol emission of adolescents voices during speaking, singing and shouting

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    Since the outbreak of the COVID-19 pandemic, singing activities for children and young people have been strictly regulated with far-reaching consequences for music education in schools and ensemble and choir singing in some places. This is also due to the fact, that there has been no reliable data available on aerosol emissions from adolescents speaking, singing, and shouting. By utilizing a laser particle counter in cleanroom conditions we show, that adolescents emit fewer aerosol particles during singing than what has been known so far for adults. In our data, the emission rates ranged from 16 P/s to 267 P/s for speaking, 141 P/s to 1240 P/s for singing, and 683 P/s to 4332 P/s for shouting. The data advocate an adaptation of existing risk management strategies and rules of conduct for groups of singing adolescents, like gatherings in an educational context, e.g. singing lessons or choir rehearsals

    Predictive MGMT status in a homogeneous cohort of IDH wildtype glioblastoma patients

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    Methylation of the O(6)-Methylguanine-DNA methyltransferase (MGMT) promoter is predictive for treatment response in glioblastoma patients. However, precise predictive cutoff values to distinguish "MGMT methylated" from "MGMT unmethylated" patients remain highly debated in terms of pyrosequencing (PSQ) analysis. We retrospectively analyzed a clinically and molecularly very well-characterized cohort of 111 IDH wildtype glioblastoma patients, who underwent gross total tumor resection and received standard Stupp treatment. Detailed clinical parameters were obtained. Predictive cutoff values for MGMT promoter methylation were determined using ROC curve analysis and survival curve comparison using Log-rank (Mantel-Cox) test. MGMT status was analyzed using pyrosequencing (PSQ), semi-quantitative methylation specific PCR (sqMSP) and direct bisulfite sequencing (dBiSeq). Highly methylated (> 20%) MGMT correlated with significantly improved progression-free survival (PFS) and overall survival (OS) in our cohort. Median PFS was 7.2 months in the unmethylated group (UM, 20% mean methylation). Median OS was 13.4 months for UM, 17.9 months for LM and 29.93 months for HM. Within the LM group, correlation of PSQ and sqMSP or dBiSeq was only conclusive in 51.5% of our cases. ROC curve analysis revealed superior test precision for survival if additional sqMSP results were considered (AUC = 0.76) compared to PSQ (cutoff 10%) alone (AUC = 0.67). We therefore challenge the widely used, strict PSQ cutoff at 10% which might not fully reflect the clinical response to alkylating agents and suggest applying a second method for MGMT testing (e.g. MSP) to confirm PSQ results for patients with LM MGMT levels if therapeutically relevant
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