Comparison of the Calibration Standards of Three Commercially Available Multiplex Kits for Human Cytokine Measurement to WHO Standards Reveals Striking Differences

Serum parameters as indicators for the efficacy of therapeutic drugs are currently in the focus of intensive research. The induction of certain cytokines (or cytokine patterns) is known to be related to the status of the immune response e.g. in regulating the TH1/TH2 balance. Regarding their potential value as surrogate parameters in clinical trials and subsequently for the assignment of treatment efficacy, the accurate and reliable determination of cytokines in patient serum is mandatory. Because serum samples are precious and limited, test methods—like the xMAP multiplex technology—that allow for the simultaneous determination of a variety of cytokines from only a small sample aliquot, can offer great advantages

The neuronal correlates of mirror illusion in children with spastic hemiparesis: a study with functional magnetic resonance imaging.

To investigate the neuronal activation pattern underlying the effects of mirror illusion in children/adolescents with normal motor development and in children/adolescents with hemiparesis and preserved contralateral corticospinal organisation. The type of cortical reorganisation was classified according to results of transcranial magnetic stimulation. Only subjects with congenital lesions and physiological contralateral cortical reorganisation were included. Functional magnetic resonance imaging was performed to investigate neuronal activation patterns with and without a mirror box. Each test consisted of a unimanual and a bimanual motor task. Seven children/adolescents with congenital hemiparesis (10-20 years old, three boys and four girls) and seven healthy subjects (8-17 years old, four boys and three girls) participated in this study. In the bimanual experiment, children with hemiparesis showed a significant effect of the mirror illusion (p<0.001 at voxel level, family-wise error corrected at cluster level) in the dorsolateral prefrontal cortex and anterior cingulate cortex of the affected and unaffected hemispheres, respectively. No significant effects of the mirror illusion were observed in unimanual experiments and in healthy participants. Mirror illusion in children/adolescents with hemiparesis leads to activation of brain areas involved in visual conflict detection and cognitive control to resolve this conflict. This effect is observed only in bimanual training. We consider that for mirror therapy in children and adolescents with hemiparesis a bimanual approach is more suitable than a unimanual approach

Het voeren van vleesvarkens met een voerstation

Voerstations met individuele dierherkenning zijn aantrekkelijk voor onderzoek bij vleesvarkens. Het is mogelijk om het voeropnamegedrag te registreren, de voeropname te beperken en de voersamenstelling te sturen. Voor de praktijk zijn ze echter name te beperken en de voersamenstelling niet geschikt vanwege de hoge kosten

Around consensual non-monogamies – assessing attitudes toward non-exclusive relationships

Consensual non-monogamy is a term used to describe intimate romantic relationships which are sexually and/or emotionally non-exclusive. The present study examined the social norms which are violated by different forms of consensual nonmonogamy,and the negative judgements that result. We asked 375 participants to rate hypothetical vignettes of people involved in one of five relationship types (monogamy, polyamory, an open relationship, swinging, and cheating) on items related to relationship satisfaction, morality, and cognitive abilities. The monogamous couple was perceived most favourably, followed by the polyamorous couple, then the open and swinging couples who were rated equally. Participants judged the cheating couple most negatively. Although social norms of sexual and emotional monogamy are important, we conclude that the aspect that has the most effect on judgements is whether the relationship structure has been agreed to by all parties

THE EVOLUTION OF MODELLING PRACTICES ON CANADA’S PARLIAMENT HILL: AN ANALYSIS OF THREE SIGNIFICANT HERITAGE BUILDING INFORMATION MODELS (HBIM)

In this paper, we explore the evolution of modelling practices used to develop three significant Heritage Building Information Models (HBIM) on Canada’s Parliament Hill National Historic Site – West Block, Centre Block, and The Library of Parliament. The unique scope, objective, and timeline for each model required an in-depth analysis to select the appropriate classification for Level of Detail (LOD) and Level of Accuracy (LOA). With each project, the refinement of modelling practices and workflows evolved, culminating in one of our most complex and challenging projects – the Library of Parliament BIM. The purpose of this paper is to share ideas and lessons learned for the intricate challenges that emerge when using LOD and LOA classifications including trade-offs between model performance, tolerances, and anticipated BIM use. In addition, we will evaluate how these decisions effected managing the digitization, data processing, data synthesis, and visualisation of the models

Trends in Outcomes of Major Intracerebral Haemorrhage in a National Cohort of Very Preterm Born Infants in Switzerland

Background: Major brain lesions, such as grade 3 intraventricular haemorrhage (G3-IVH) and periventricular haemorrhagic infarction (PVHI) are among the main predictors for poor neurodevelopment in preterm infants. In the last decades advancements in neonatal care have led to a general decrease in adverse outcomes. Aim: To assess trends of mortality and neurodevelopmental impairment (NDI) in a recent Swiss cohort of very preterm infants with grade 3 intraventricular haemorrhage (G3-IVH) and periventricular haemorrhagic infarction (PVHI). Methods: In this retrospective population-based cohort study, rates of mortality, and NDI at 2 years corrected age were reported in infants born at 24–29 weeks gestational age (GA) in Switzerland in 2002–2014, with G3-IVH and/or PVHI. Results: Out of 4956 eligible infants, 462 (9%) developed G3-IVH (n = 172) or PVHI (n = 290). The average mortality rates for the two pathologies were 33% (56/172) and 60% (175/290), respectively. In 2002–2014, no change in rates of mortality (G3-IVH, p = 0.845; PVHI, p = 0.386) or NDI in survivors (G3-IVH, p = 0.756; PVHI, p = 0.588) were observed, while mean GA decreased (G3-IVH, p = 0.020; PVHI, p = 0.004). Multivariable regression analysis showed a strong association of G3-IVH and PVHI for both mortality and NDI. Death occurred after withdrawal of care in 81% of cases. Conclusion: In 2002–2014, rates of mortality and NDI in very preterm born infants with major brain lesions did not change. The significant decrease in mean GA and changing hospital policies over this time span may factor into the interpretation of these results

International symposium: "Evolution of permian marine biota," and problems concerning permian sections in the type region

The main results of the International Symposium "Evolution of Permian Marine Biota," are presented. The Artinskian to Ufimian part of the section at the Kozhim River (Polar Urals) is briefly described including its paleontological characteristics. Potentials for further study of Permian deposits in the Urals and possibilities of using the Uralian stages as international standards are discussed. Copyright © 1997 by MAHK Hayka/Interperiodica Publishing

Multi-level suppression of receptor-PI3K-mTORC1 by fatty acid synthase inhibitors is crucial for their efficacy against ovarian cancer cells

Receptor-PI3K-mTORC1 signaling and fatty acid synthase (FASN)-regulated lipid biosynthesis harbor numerous drug targets and are molecularly connected. We hypothesize that unraveling the mechanisms of pathway cross-talk will be useful for designing novel co-targeting strategies for ovarian cancer (OC). The impact of receptor-PI3K-mTORC1 onto FASN is already well-characterized. However, reverse actions–from FASN towards receptor-PI3K-mTORC1–are still elusive. We show that FASN-blockade impairs receptor-PI3K-mTORC1 signaling at multiple levels. Thin-layer chromatography and MALDI-MS/MS reveals that FASN-inhibitors (C75, G28UCM) augment polyunsaturated fatty acids and diminish signaling lipids diacylglycerol (DAG) and phosphatidylinositol 3,4,5-trisphosphate (PIP3) in OC cells (SKOV3, OVCAR-3, A2780, HOC-7). Western blotting and micropatterning demonstrate that FASN-blockers impair phosphorylation/expression of EGF-receptor/ERBB/HER and decrease GRB2–EGF-receptor recruitment leading to PI3K-AKT suppression. FASN-inhibitors activate stress response-genes HIF-1α-REDD1 (RTP801/DIG2/DDIT4) and AMPKα causing mTORC1- and S6-repression. We conclude that FASN-inhibitor-mediated blockade of receptor-PI3K-mTORC1 occurs due to a number of distinct but cooperating processes. Moreover, decrease of PI3K-mTORC1 abolishes cross-repression of MEK-ERK causing ERK activation. Consequently, the MEK-inhibitor selumetinib/AZD6244, in contrast to the PI3K/mTOR-inhibitor dactolisib/NVP-BEZ235, increases growth inhibition when given together with a FASN-blocker. We are the first to provide deep insight on how FASN-inhibition blocks ERBB-PI3K-mTORC1 activity at multiple molecular levels. Moreover, our data encourage therapeutic approaches using FASN-antagonists together with MEK-ERK-inhibitors