Comprehensive Nuclear-Test-Ban Treaty – a peace-keeping initiative with scientific impact

Any major shaking of the Earth can be recorded on a seismograph regardless of the nature of the source. Earthquakes and large explosions generate waves with similar frequency content. This fact has been used for decades to construct systems to monitor detonations of underground nuclear explosions. The quality of the monitoring system has increased significantly in recent years, and we demonstrate here that the data are useful in Danish earthquake research

MicroRNA-145 Targets YES and STAT1 in Colon Cancer Cells

BACKGROUND: MicroRNAs (miRNAs) have emerged as important gene regulators and are recognized as key players in tumorigenesis. miR-145 is reported to be down-regulated in several cancers, but knowledge of its targets in colon cancer remains limited. METHODOLOGY/PRINCIPAL FINDINGS: To investigate the role of miR-145 in colon cancer, we have employed a microarray based approach to identify miR-145 targets. Based on seed site enrichment analyses and unbiased word analyses, we found a significant enrichment of miRNA binding sites in the 3'-untranslated regions (UTRs) of transcripts down-regulated upon miRNA overexpression. Gene Ontology analysis showed an overrepresentation of genes involved in cell death, cellular growth and proliferation, cell cycle, gene expression and cancer. A number of the identified miRNA targets have previously been implicated in cancer, including YES, FSCN1, ADAM17, BIRC2, VANGL1 as well as the transcription factor STAT1. Both YES and STAT1 were verified as direct miR-145 targets. CONCLUSIONS/SIGNIFICANCE: The study identifies and validates new cancer-relevant direct targets of miR-145 in colon cancer cells and hereby adds important mechanistic understanding of the tumor-suppressive functions of miR-145

Mitochondrial proteomics on human fibroblasts for identification of metabolic imbalance and cellular stress

<p>Abstract</p> <p>Background</p> <p>Mitochondrial proteins are central to various metabolic activities and are key regulators of apoptosis. Disturbance of mitochondrial proteins is therefore often associated with disease. Large scale protein data are required to capture the mitochondrial protein levels and mass spectrometry based proteomics is suitable for generating such data. To study the relative quantities of mitochondrial proteins in cells from cultivated human skin fibroblasts we applied a proteomic method based on nanoLC-MS/MS analysis of iTRAQ-labeled peptides.</p> <p>Results</p> <p>When fibroblast cultures were exposed to mild metabolic stress – by cultivation in galactose medium- the amount of mitochondria appeared to be maintained whereas the levels of individual proteins were altered. Proteins of respiratory chain complex I and IV were increased together with NAD⁺-dependent isocitrate dehydrogenase of the citric acid cycle illustrating cellular strategies to cope with altered energy metabolism. Furthermore, quantitative protein data, with a median standard error below 6%, were obtained for the following mitochondrial pathways: fatty acid oxidation, citric acid cycle, respiratory chain, antioxidant systems, amino acid metabolism, mitochondrial translation, protein quality control, mitochondrial morphology and apoptosis.</p> <p>Conclusion</p> <p>The robust analytical platform in combination with a well-defined compendium of mitochondrial proteins allowed quantification of single proteins as well as mapping of entire pathways. This enabled characterization of the interplay between metabolism and stress response in human cells exposed to mild stress.</p

IMECE2008-67360 GASTROESOPHAGEAL REFLUX 2D AND 3D STEADY STATE CFD SIMULATIONS

ABSTRACT Gastro-Esophageal Reflux Disease (GERD) is a condition which affects up to 20% of the adult US population on a weekly basis. It is a condition where acid is allowed to flow from the stomach and into the esophagus where it causes damage to the local tissue. In chronic cases the condition can lead to cancer. Dysfunction of the Esophagogastric Junction is indicated as a primary cause. The recently developed Functional Lumen Imaging Probe (FLIP) is designed for assessment of the EGJ. It measures the cross sectional area at eight locations through the junction. This data has been used to construct a series of computational fluid dynamic simulations. These simulations showed a jet of fluid which squirts into the esophagus under the gastric pressure. This jet corresponds with previously gathered anecdotal evidence. The centerline velocities of this jet were measured and this suggested that the jet could travel up to 20 times the minimum diameter of the EGJ into the esophagus before decelerating to 25% of its original velocity. This means that if an EGJ was curved then this jet could impinge on the walls causing a localized area of increased damage to the mucosa compared to the surrounding tissue

Tailoring temporal description logics for reasoning over temporal conceptual models

Temporal data models have been used to describe how data can evolve in the context of temporal databases. Both the Extended Entity-Relationship (EER) model and the Unified Modelling Language (UML) have been temporally extended to design temporal databases. To automatically check quality properties of conceptual schemas various encoding to Description Logics (DLs) have been proposed in the literature. On the other hand, reasoning on temporally extended DLs turn out to be too complex for effective reasoning ranging from 2ExpTime up to undecidable languages. We propose here to temporalize the ‘light-weight’ DL-Lite logics obtaining nice computational results while still being able to represent various constraints of temporal conceptual models. In particular, we consider temporal extensions of DL-Lite^N_bool, which was shown to be adequate for capturing non-temporal conceptual models without relationship inclusion, and its fragment DL-Lite^N_core with most primitive concept inclusions, which are nevertheless enough to represent almost all types of atemporal constraints (apart from covering)

Identification of a protein encoded in the EB-viral open reading frame BMRF2

Using monospecific rabbit sera against a peptide derived from a potential antigenic region of the Epstein-Barr viral amino acid sequence encoded in the open reading frame BMRF2 we could identify a protein-complex of 53/55 kDa in chemically induced B95-8, P3HR1 and Raji cell lines. This protein could be shown to be membrane-associated, as predicted by previous computer analysis of the secondary structure and hydrophilicity pattern, and may be a member of EBV-induced membrane proteins in lytically infected cells

Fine mapping seronegative and seropositive rheumatoid arthritis to shared and distinct HLA alleles by adjusting for the effects of heterogeneity

Despite progress in defining human leukocyte antigen (HLA) alleles for anti-citrullinated-protein-autoantibody-positive (ACPA(+)) rheumatoid arthritis (RA), identifying HLA alleles for ACPA-negative (ACPA(-)) RA has been challenging because of clinical heterogeneity within clinical cohorts. We imputed 8,961 classical HLA alleles, amino acids, and SNPs from Immunochip data in a discovery set of 2,406 ACPA(-) RA case and 13,930 control individuals. We developed a statistical approach to identify and adjust for clinical heterogeneity within ACPA(-) RA and observed independent associations for serine and leucine at position 11 in HLA-DRbeta1 (p = 1.4 x 10(-13), odds ratio [OR] = 1.30) and for aspartate at position 9 in HLA-B (p = 2.7 x 10(-12), OR = 1.39) within the peptide binding grooves. These amino acid positions induced associations at HLA-DRB1( *)03 (encoding serine at 11) and HLA-B( *)08 (encoding aspartate at 9). We validated these findings in an independent set of 427 ACPA(-) case subjects, carefully phenotyped with a highly sensitive ACPA assay, and 1,691 control subjects (HLA-DRbeta1 Ser11+Leu11: p = 5.8 x 10(-4), OR = 1.28; HLA-B Asp9: p = 2.6 x 10(-3), OR = 1.34). Although both amino acid sites drove risk of ACPA(+) and ACPA(-) disease, the effects of individual residues at HLA-DRbeta1 position 11 were distinct (p \u3c 2.9 x 10(-107)). We also identified an association with ACPA(+) RA at HLA-A position 77 (p = 2.7 x 10(-8), OR = 0.85) in 7,279 ACPA(+) RA case and 15,870 control subjects. These results contribute to mounting evidence that ACPA(+) and ACPA(-) RA are genetically distinct and potentially have separate autoantigens contributing to pathogenesis. We expect that our approach might have broad applications in analyzing clinical conditions with heterogeneity at both major histocompatibility complex (MHC) and non-MHC regions

Review: ‘Gimme five’: future challenges in multiple sclerosis. ECTRIMS Lecture 2009

This article is based on the ECTRIMS lecture given at the 25th ECTRIMS meeting which was held in Düsseldorf, Germany, from 9 to 12 September 2009. Five challenges have been identified: (1) safeguarding the principles of medical ethics; (2) optimizing the risk/benefit ratio; (3) bridging the gap between multiple sclerosis and experimental autoimmune encephalitis; (4) promoting neuroprotection and repair; and (5) tailoring multiple sclerosis therapy to the individual patient. Each of these challenges will be discussed and placed in the context of current research into the pathogenesis and treatment of multiple sclerosis

Absolute dimensions of eclipsing binaries. XXVIII. BK Pegasi and other F-type binaries: Prospects for calibration of convective core overshoot

We present a detailed study of the F-type detached eclipsing binary BK Peg, based on new photometric and spectroscopic observations. The two components, which have evolved to the upper half of the main-sequence band, are quite different with masses and radii of (1.414 +/- 0.007 Msun, 1.988 +/- 0.008 Rsun) and (1.257 +/- 0.005 Msun, 1.474 +/- 0.017 Rsun), respectively. The 5.49 day period orbit of BK Peg is slightly eccentric (e = 0.053). The measured rotational velocities are 16.6 +/- 0.2 (primary) and 13.4 +/- 0.2 (secondary) km/s. For the secondary component this corresponds to (pseudo)synchronous rotation, whereas the primary component seems to rotate at a slightly lower rate. We derive an iron abundance of [Fe/H] =-0.12 +/- 0.07 and similar abundances for Si, Ca, Sc, Ti, Cr and Ni. Yonsei-Yale and Victoria-Regina evolutionary models for the observed metal abundance reproduce BK Peg at ages of 2.75 and 2.50 Gyr, respectively, but tend to predict a lower age for the more massive primary component than for the secondary. We find the same age trend for three other upper main-sequence systems in a sample of well studied eclipsing binaries with components in the 1.15-1.70 Msun range, where convective core overshoot is gradually ramped up in the models. We also find that the Yonsei-Yale models systematically predict higher ages than the Victoria-Regina models. The sample includes BW Aqr, and as a supplement we have determined a [Fe/H] abundance of -0.07 +/- 0.11 for this late F-type binary. We propose to use BK Peg, BW Aqr, and other well-studied 1.15-1.70 Msun eclipsing binaries to fine-tune convective core overshoot, diffusion, and possibly other ingredients of modern theoretical evolutionary models.Comment: Accepted for publication in Astronomy and Astrophysic