Dynamical difference between the cD galaxy and the stellar diffuse component in simulated galaxy clusters

Member galaxies within galaxy clusters nowadays can be routinely identified in cosmological, hydrodynamical simulations using methods based on identifying self bound, locally over dense substructures. However, distinguishing the central galaxy from the stellar diffuse component within clusters is notoriously difficult, and in the center it is not even clear if two distinct stellar populations exist. Here, after subtracting all member galaxies, we use the velocity distribution of the remaining stars and detect two dynamically, well-distinct stellar components within simulated galaxy clusters. These differences in the dynamics can be used to apply an un-binding procedure which leads to a spatial separation of the two components into a cD and a diffuse stellar component (DSC). Applying our new algorithm to a cosmological, hydrodynamical simulation we find that -- in line with previous studies -- these two components have clearly distinguished spatial and velocity distributions as well as different star formation histories. We show that the DSC fraction -- which can broadly be associated with the observed intra cluster light -- does not depend on the virial mass of the galaxy cluster and is much more sensitive to the formation history of the cluster. We conclude that the separation of the cD and the DSC in simulations, based on our dynamical criteria, is more physically motivated than current methods which depend on implicit assumptions on a length scale associated with the cD galaxy and therefore represent a step forward in understanding the different stellar components within galaxy clusters. Our results also show the importance of analyzing the dynamics of the DSC to characterize its properties and understand its origin.Comment: 15 pages, 18 figures, MNRAS in pres

Visualization of plasmid delivery to keratinocytes in mouse and human epidermis

The accessibility of skin makes it an ideal target organ for nucleic acid-based therapeutics; however, effective patient-friendly delivery remains a major obstacle to clinical utility. A variety of limited and inefficient methods of delivering nucleic acids to keratinocytes have been demonstrated; further advances will require well-characterized reagents, rapid noninvasive assays of delivery, and well-developed skin model systems. Using intravital fluorescence and bioluminescence imaging and a standard set of reporter plasmids we demonstrate transfection of cells in mouse and human xenograft skin using intradermal injection and two microneedle array delivery systems. Reporter gene expression could be detected in individual keratinocytes, in real-time, in both mouse skin as well as human skin xenografts. These studies revealed that non-invasive intravital imaging can be used as a guide for developing gene delivery tools, establishing a benchmark for comparative testing of nucleic acid skin delivery technologies

Persistence of anticancer activity in berry extracts after simulated gastrointestinal digestion and colonic fermentation

Fruit and vegetable consumption is associated at the population level with a protective effect against colorectal cancer. Phenolic compounds, especially abundant in berries, are of interest due to their putative anticancer activity. After consumption, however, phenolic compounds are subject to digestive conditions within the gastrointestinal tract that alter their structures and potentially their function. However, the majority of phenolic compounds are not efficiently absorbed in the small intestine and a substantial portion pass into the colon. We characterized berry extracts (raspberries, strawberries, blackcurrants) produced by in vitro-simulated upper intestinal tract digestion and subsequent fecal fermentation. These extracts and selected individual colonic metabolites were then evaluated for their putative anticancer activities using in vitro models of colorectal cancer, representing the key stages of initiation, promotion and invasion. Over a physiologically-relevant dose range (0–50 µg/ml gallic acid equivalents), the digested and fermented extracts demonstrated significant anti-genotoxic, anti-mutagenic and anti-invasive activity on colonocytes. This work indicates that phenolic compounds from berries undergo considerable structural modifications during their passage through the gastrointestinal tract but their breakdown products and metabolites retain biological activity and can modulate cellular processes associated with colon cancer

Reversal of infall in SgrB2(M) revealed by Herschel/HIFI observations of HCN lines at THz frequencies

To investigate the accretion and feedback processes in massive star formation, we analyze the shapes of emission lines from hot molecular cores, whose asymmetries trace infall and expansion motions. The high-mass star forming region SgrB2(M) was observed with Herschel/HIFI (HEXOS key project) in various lines of HCN and its isotopologues, complemented by APEX data. The observations are compared to spherically symmetric, centrally heated models with density power-law gradient and different velocity fields (infall or infall+expansion), using the radiative transfer code RATRAN. The HCN line profiles are asymmetric, with the emission peak shifting from blue to red with increasing J and decreasing line opacity (HCN to H$^{13}$CN). This is most evident in the HCN 12--11 line at 1062 GHz. These line shapes are reproduced by a model whose velocity field changes from infall in the outer part to expansion in the inner part. The qualitative reproduction of the HCN lines suggests that infall dominates in the colder, outer regions, but expansion dominates in the warmer, inner regions. We are thus witnessing the onset of feedback in massive star formation, starting to reverse the infall and finally disrupting the whole molecular cloud. To obtain our result, the THz lines uniquely covered by HIFI were critically important.Comment: A&A, HIFI special issue, accepte

Mutations in Subunits of the Activating Signal Cointegrator 1 Complex Are Associated with Prenatal Spinal Muscular Atrophy and Congenital Bone Fractures

Transcriptional signal cointegrators associate with transcription factors or nuclear receptors and coregulate tissue-specific gene transcription. We report on recessive loss-of-function mutations in two genes (TRIP4 and ASCC1) that encode subunits of the nuclear activating signal cointegrator 1 (ASC-1) complex. We used autozygosity mapping and whole-exome sequencing to search for pathogenic mutations in four families. Affected individuals presented with prenatal-onset spinal muscular atrophy (SMA), multiple congenital contractures (arthrogryposis multiplex congenita), respiratory distress, and congenital bone fractures. We identified homozygous and compound-heterozygous nonsense and frameshift TRIP4 and ASCC1 mutations that led to a truncation or the entire absence of the respective proteins and cosegregated with the disease phenotype. Trip4 and Ascc1 have identical expression patterns in 17.5-day-old mouse embryos with high expression levels in the spinal cord, brain, paraspinal ganglia, thyroid, and submandibular glands. Antisense morpholino-mediated knockdown of either trip4 or ascc1 in zebrafish disrupted the highly patterned and coordinated process of α-motoneuron outgrowth and formation of myotomes and neuromuscular junctions and led to a swimming defect in the larvae. Immunoprecipitation of the ASC-1 complex consistently copurified cysteine and glycine rich protein 1 (CSRP1), a transcriptional cofactor, which is known to be involved in spinal cord regeneration upon injury in adult zebrafish. ASCC1 mutant fibroblasts downregulated genes associated with neurogenesis, neuronal migration, and pathfinding (SERPINF1, DAB1, SEMA3D, SEMA3A), as well as with bone development (TNFRSF11B, RASSF2, STC1). Our findings indicate that the dysfunction of a transcriptional coactivator complex can result in a clinical syndrome affecting the neuromuscular system

Herschel observations of extra-ordinary sources: Detecting spiral arm clouds by CH absorption lines

We have observed CH absorption lines ($J=3/2, N=1 \leftarrow J=1/2, N=1$) against the continuum source Sgr~B2(M) using the \textit{Herschel}/HIFI instrument. With the high spectral resolution and wide velocity coverage provided by HIFI, 31 CH absorption features with different radial velocities and line widths are detected and identified. The narrower line width and lower column density clouds show `spiral arm' cloud characteristics, while the absorption component with the broadest line width and highest column density corresponds to the gas from the Sgr~B2 envelope. The observations show that each `spiral arm' harbors multiple velocity components, indicating that the clouds are not uniform and that they have internal structure. This line-of-sight through almost the entire Galaxy offers unique possibilities to study the basic chemistry of simple molecules in diffuse clouds, as a variety of different cloud classes are sampled simultaneously. We find that the linear relationship between CH and H$_2$ column densities found at lower $A_V$ by UV observations does not continue into the range of higher visual extinction. There, the curve flattens, which probably means that CH is depleted in the denser cores of these clouds.Comment: Accepted for publication in A&A, HIFI Special Issu

Considering Intra-individual Genetic Heterogeneity to Understand Biodiversity

In this chapter, I am concerned with the concept of Intra-individual Genetic Hetereogeneity (IGH) and its potential influence on biodiversity estimates. Definitions of biological individuality are often indirectly dependent on genetic sampling -and vice versa. Genetic sampling typically focuses on a particular locus or set of loci, found in the the mitochondrial, chloroplast or nuclear genome. If ecological function or evolutionary individuality can be defined on the level of multiple divergent genomes, as I shall argue is the case in IGH, our current genetic sampling strategies and analytic approaches may miss out on relevant biodiversity. Now that more and more examples of IGH are available, it is becoming possible to investigate the positive and negative effects of IGH on the functioning and evolution of multicellular individuals more systematically. I consider some examples and argue that studying diversity through the lens of IGH facilitates thinking not in terms of units, but in terms of interactions between biological entities. This, in turn, enables a fresh take on the ecological and evolutionary significance of biological diversity

Surface pretreatment for prolonged survival of cemented tibial prosthesis components: full- vs. surface-cementation technique

BACKGROUND: One of few persisting problems of cemented total knee arthroplasty (TKA) is aseptic loosening of tibial component due to degradation of the interface between bone cement and metallic tibial shaft component, particularly for surface cemented tibial components. Surface cementation technique has important clinical meaning in case of revision and for avoidance of stress shielding. Degradation of the interface between bone cement and bone may be a secondary effect due to excessive crack formation in bone cement starting at the opposite metallic surface. METHODS: This study was done to prove crack formation in the bone cement near the metallic surface when this is not coated. We propose a newly developed coating process by PVD layering with SiO(x )to avoid that crack formation in the bone cement. A biomechanical model for vibration fatigue test was done to simulate the physiological and biomechanical conditions of the human knee joint and to prove excessive crack formation. RESULTS: It was found that coated tibial components showed a highly significant reduction of cement cracking near the interface metal/bone cement (p < 0.01) and a significant reduction of gap formation in the interface metal-to-bone cement (p < 0.05). CONCLUSION: Coating dramatically reduces hydrolytic- and stress-related crack formation at the prosthesis interface metal/bone cement. This leads to a more homogenous load transfer into the cement mantle which should reduce the frequency of loosening in the interfaces metal/bone cement/bone. With surface coating of the tibial component it should become possible that surface cemented TKAs reveal similar loosening rates as TKAs both surface and stem cemented. This would be an important clinical advantage since it is believed that surface cementing reduces metaphyseal bone loss in case of revision and stress shielding for better bone health

Measurement of the t t-bar production cross section in the dilepton channel in pp collisions at sqrt(s) = 7 TeV

The t t-bar production cross section (sigma[t t-bar]) is measured in proton-proton collisions at sqrt(s) = 7 TeV in data collected by the CMS experiment, corresponding to an integrated luminosity of 2.3 inverse femtobarns. The measurement is performed in events with two leptons (electrons or muons) in the final state, at least two jets identified as jets originating from b quarks, and the presence of an imbalance in transverse momentum. The measured value of sigma[t t-bar] for a top-quark mass of 172.5 GeV is 161.9 +/- 2.5 (stat.) +5.1/-5.0 (syst.) +/- 3.6(lumi.) pb, consistent with the prediction of the standard model.Comment: Replaced with published version. Included journal reference and DO

Search for the standard model Higgs boson in the H to ZZ to 2l 2nu channel in pp collisions at sqrt(s) = 7 TeV

A search for the standard model Higgs boson in the H to ZZ to 2l 2nu decay channel, where l = e or mu, in pp collisions at a center-of-mass energy of 7 TeV is presented. The data were collected at the LHC, with the CMS detector, and correspond to an integrated luminosity of 4.6 inverse femtobarns. No significant excess is observed above the background expectation, and upper limits are set on the Higgs boson production cross section. The presence of the standard model Higgs boson with a mass in the 270-440 GeV range is excluded at 95% confidence level.Comment: Submitted to JHE