Cosmological implications of a Dark Matter self-interaction energy density

We investigate cosmological constraints on an energy density contribution of elastic dark matter self-interactions characterized by the mass of the exchange particle and coupling constant. Because of the expansion behaviour in a Robertson-Walker metric we investigate self-interacting dark matter that is warm in the case of thermal relics. The scaling behaviour of dark matter self-interaction energy density shows that it can be the dominant contribution (only) in the very early universe. Thus its impact on primordial nucleosynthesis is used to restrict the interaction strength, which we find to be at least as strong as the strong interaction. Furthermore we explore dark matter decoupling in a self-interaction dominated universe, which is done for the self-interacting warm dark matter as well as for collisionless cold dark matter in a two component scenario. We find that strong dark matter self-interactions do not contradict super-weak inelastic interactions between self-interacting dark matter and baryonic matter and that the natural scale of collisionless cold dark matter decoupling exceeds the weak scale and depends linearly on the particle mass. Finally structure formation analysis reveals a linear growing solution during self-interaction domination; however, only non-cosmological scales are enhanced.Comment: 14 pages, 14 figures; version published in Phys. Rev.

A Specific Prebiotic Mixture Added to Starting Infant Formula Has Long-Lasting Bifidogenic Effects123

There is some evidence that early colonization of the intestine affects the composition of the intestinal microbiota after weaning. In the present study, the effect of prebiotics administered from the first day of life on fecal counts of bifidobacteria and lactobacilli were studied during and after the administration of the prebiotics. In this double-blind, randomized, placebo-controlled, explorative study, 20 newborns of hepatitis C virus-infected mothers who decided not to breast feed due to their concerns regarding their plasma viral load were randomly assigned to either a formula with 8 g/L of a specific prebiotic mixture (short-chain galacto-oligosaccharides and long-chain fructo-oligosaccharides, ratio 9:1) or a formula containing the same amount of maltodextrin (placebo). Clinical examination including anthropometric measurements, microbiological analysis of fecal samples, and blood leukocyte population analysis were performed at birth and 3, 6, and 12 mo age. At the age of 12 mo, hepatitis B vaccine-specific IgG serum titers (Hepatitis B virus surface antibodies) were also measured. Prebiotic supplementation resulted in more fecal bifidobacteria (P < 0.0001) and lactobacilli (P = 0.0044) compared with the placebo group. These differences between the groups were maintained during the second half of the first year without any prebiotic supplementation. There was no influence of the different diets on anthropometric data or the measured immunological variables. The data from this small explorative study indicate that early colonization of the intestine might have long-lasting effects on the composition of the intestinal microbiota

IDO1 is highly expressed in macrophages of patients in advanced tumour stages of oral squamous cell carcinoma

Purpose Strategies for Indolamine-2,3-dioxygenase 1 (IDO1) inhibition in cancer immunotherapy once produced encouraging results, but failed in clinical trials. Recent evidence indicates that immune cells in the tumour microenvironment, especially macrophages, contribute to immune dysregulation and therefore might play a critical role in drug resistance. Methods In this study, we investigated the signifcance of IDO1 expressing immune cells in primary tumours and corresponding lymph node metastases (LNMs) in oral squamous cell carcinoma (OSCC) by immunohistochemistry. The link between IDO1 and macrophages was investigated by fow cytometry in tumour tissue, healthy adjacent tissue and peripheral blood mononuclear cells (PBMCs). IDO1 activity (measured as Kynurenine/Tryptophan ratio) was assessed by ELISAs. Results High IDO1 expression in tumour-infltrating immune cells was signifcantly correlated with advanced stages [Spearman’s rank correlation (SRC), p=0.027] and reduced progression-free survival (multivariate Cox regression, p=0.034). IDO1 was signifcantly higher expressed in PBMCs of patients in advanced stages than in healthy controls (ANOVA, p<0.05) and IDO1+ macrophages were more abundant in intratumoural areas than peritumoural (t test, p<0.001). IDO1 expression in PBMCs was signifcantly correlated with IDO1 activity in serum (SRC, p<0.05). IDO1 activity was signifcantly higher in patients with LNMs (t test, p<0.01). Conclusion All in all, IDO1 expressing immune cells, especially macrophages, are more abundant in advanced stages of OSCC and are associated with reduced progression-free survival. Further investigations are needed to explore their role in local and systemic immune response. The IDO1 activity might be a suitable biomarker of metastasis in OSCC patients

Correcting gradient chain induced fat quantification errors in radial multi-echo Dixon imaging using a gradient modulation transfer function

Purpose: Multi-echo Stack-of-stars (SoS) radial k-space trajectories with golden angle ordering are becoming popular for free-breathing abdominal Dixon imaging and proton density fat fraction (PDFF) mapping. Gradient chain imperfections including eddy currents and system delays are known to affect the image quality of radial imaging and to confound the estimation of PDFF mapping. This work proposes a retrospective trajectory correction method based on a simple gradient modulation transfer function (GMTF) measurement to predict and correct gradient chain induced k-space trajectory errors.Methods: The GMTF was measured using the standard hardware of a 3 Tesla scanner on a phantom using the thin slice method and was applied to a 3D radial SoS Dixon imaging sequence. The impact of the GMTF-based correction on image reconstruction and PDFF quantification was investigated using numerical simulations and validated on experimental phantom data as well as on in vivo leg and liver data of healthy volunteers.Results: Correcting the k-space trajectories with the measured GMTF during image reconstruction reduced PDFF quantification errors for phantom and in vivo acquisitions. A Bland-Altman comparison of the measured PDFF phantom and reference data confirmed that the GMTF correction narrowed down the limits of agreement (LoA) from 1.3% ± 8.1% (uncorrected) to 1.9% ± 5.4% (GMTF-corrected) over the full PDFF range (0%–100%) and from −0.26% ± 2.8% (uncorrected) to 0.12% ± 1.5% (GMTF-corrected) within the 0%–50% PDFF range. Liver PDFF estimation was improved by reducing the standard deviation of the mean liver PDFF and the bias of the mean liver PDFF for all subjects.Conclusion: The proposed GMTF-based k-space trajectory correction is a fast alternative method for avoiding PDFF quantitation errors caused by gradient-system induced k-space trajectory errors in 3D radial multi-echo gradient-echo acquisitions

Cy Twombly. Bild, Text, Paratext

Die Bildwerke des US-amerikanischen Künstlers Cy Twombly (1928–2011) gelten als hermetisch und schwer zugänglich. Bleistiftgekritzel, Farbballungen, taumelnde Linien, einander überlagernde Farbschichten und Einschreibungen, geometrische Figuren, Zahlen, Zahlenreihen, Wörter, Zitatfragmente und rätselhafte Bildtitel stellen Forscher wie Betrachter vor ganz besondere Herausforderungen. Gemäß der interdisziplinär-transkulturellen Forschungsmethode des Internationalen Kollegs Morphomata an der Universität zu Köln versammelte im Juni 2012 ein Kongress neben Kunsthistorikern auch namhafte Fachleute aus den Bereichen Ägyptologie, Archäologie, Germanistik, Gräzistik, Anglistik, Japanologie und Romanistik, d.h. all jenen Fachgebieten und Kulturkreisen, die eine Inspirationsquelle für das OEuvre Cy Twomblys darstellten. Befragen diese den Bezug zwischen Werktitel, Werk und eingeschriebenen Zitaten, so legen führende Vertreter der Twomblyforschung den Fokus auf Bildsprache und Schriftbildlichkeit bei Cy Twombly. Durch umfassende Deutungen berühmter Einzelwerke und Werkgruppen in sämtlichen von Twombly angewandten künstlerischen Medien erschließt der Band in einem fächerübergreifenden Blick einen Zugang zur assoziativ-referentiellen Bildsprache Cy Twomblys

Cy Twombly. Image, Text, Paratext

The artworks of the US artist Cy Twombly (1928–2011) are considered to be hermetic and inaccessible. Pencil scribblings, explosions of paint, tumbling lines, overlapping layers of color, and inscriptions, geometrical figures, numerals, rows of numbers, words, fragments of quotations, and enigmatic work-titles present very special challenges to both researchers and viewers. In the interdisciplinary and transcultural research method of the Morphomata International Center for Advanced Studies at the University of Cologne, a conference was held in June 2012 that brought art historians together with renowned scholars of Egyptology, Archaeology, German, Greek, English, Japanese, and the Romance languages, i.e. all the fields and cultural spheres that were a source of inspiration for the œuvre of Cy Twombly. While these scholars inquire into the relation between title, work, and inscribed quotations, leading representatives of research on Twombly focus on the visual language and scriptural-imagistic quality of Cy Twombly’s work. Through comprehensive interpretations of famous single works and groups in all the artistic media employed by Twombly, the volume’s cross-disciplinary view opens up a route into the associative-referential visual language of Cy Twombly

Expression of cathepsin K and MMP-1 indicate persistent osteodestruktive activity in longstanding ankylosing spondylitis

Abstract Background. Ankylosing spondylitis (AS) is a frequent largely genetically determined rheumatic disease that is characterised by spinal inflammation and new bone formation. However, the exact pathogenesis including pathology is still not clear. Objective. To analyse tissue obtained at spinal surgery by immunohistochemistry and compare the specimen of patients with AS to those with degenerative disc disease (DDD). Methods. Bony and soft tissue specimens of 30 AS and 20 DDD patients were obtained during spinal osteotomy from different anatomic regions including articular and spinous processes, interspinous ligaments and intervertebral disks. Immunohistolochemistry was performed with established markers for cathepsin-K, MMP-1, MMP-3 and RANK-ligand. Results. Cathepsin-K and MMP-1-positive cells were only observed in AS specimen. Cathepsin-K-positive multinucleated cells were detected at articular processes adjacent to fibrous tissues. MMP-1 was expressed in smaller mononuclear cells attached to bone, Invasion of bone by MMP-1 cells was seen at entheseal sites. In the intervertebral disks, most mononuclear cells were cathepsin-K-positive. Isolated cells expressing these matrix degrading enzymes found in DDD never showed signs of invasion. No differences were found for MMP-3 between AS and DDD. Clear expression of RANK ligand was only detected in one AS patient

Specification of the NF-κB transcriptional response by p65 phosphorylation and TNF-induced nuclear translocation of IKKε

Here we investigated the regulation of NF-κB activity by post-translational modifications upon reconstitution of NF-κB p65-deficient cells with the wild-type protein or phosphorylation-defect mutants. Analysis of NF-κB target gene expression showed that p65 phosphorylations alone or in combination function to direct transcription in a highly target gene-specific fashion, a finding discussed here as the NF-κB barcode hypothesis. High-resolution microscopy and surface rendering revealed serine 536 phosphorylated p65 predominantly in the cytosol, while serine 468 phosphorylated p65 mainly localized in nuclear speckles. TNF stimulation resulted in the translocation of the cytosolic p65 kinase IKKε to the nucleus and also to promyelocytic leukemia (PML) nuclear bodies. This inducible IKKε translocation was dependent on p65 phosphorylation and was prevented by the oncogenic PML-RARα fusion protein. Chromatin immunoprecipitation experiments revealed the inducible association of IKKε to the control regions of several NF-κB target genes. In the nucleus, the kinase contributes to the expression of a subset of NF-κB-regulated genes, thus revealing a novel role of IKKε for the control of nuclear NF-κB activity

Microfluidic Systems for Pathogen Sensing: A Review

Rapid pathogen sensing remains a pressing issue today since conventional identification methodsare tedious, cost intensive and time consuming, typically requiring from 48 to 72 h. In turn, chip based technologies, such as microarrays and microfluidic biochips, offer real alternatives capable of filling this technological gap. In particular microfluidic biochips make the development of fast, sensitive and portable diagnostic tools possible, thus promising rapid and accurate detection of a variety of pathogens. This paper will provide a broad overview of the novel achievements in the field of pathogen sensing by focusing on methods and devices that compliment microfluidics