Resonant Kelvin-Helmholtz modes in sheared relativistic flows

Qualitatively new aspects of the (linear and non-linear) stability of sheared relativistic (slab) jets are analyzed. The linear problem has been solved for a wide range of jet models well inside the ultrarelativistic domain (flow Lorentz factors up to 20; specific internal energies $\approx 60c^2$). As a distinct feature of our work, we have combined the analytical linear approach with high-resolution relativistic hydrodynamical simulations, which has allowed us i) to identify, in the linear regime, resonant modes specific to the relativistic shear layer ii) to confirm the result of the linear analysis with numerical simulations and, iii) more interestingly, to follow the instability development through the non-linear regime. We find that very high-order reflection modes with dominant growth rates can modify the global, long-term stability of the relativistic flow. We discuss the dependence of these resonant modes on the jet flow Lorentz factor and specific internal energy, and on the shear layer thickness. The results could have potential applications in the field of extragalactic relativistic jets.Comment: Accepted for publication in Physical Review E. For better quality images, please check http://www.mpifr-bonn.mpg.de/staff/mperucho/Research.htm

Catching the radio flare in CTA 102. II. VLBI kinematic analysis

Context. Very Long Baseline Interferometry (VLBI) observations can resolve the radio structure of Active Galactic Nuclei (AGN) and provide estimates of the structural and kinematic characteristics at parsec-scales in their jets. The changes in the kinematics of the observed jet features can be used to study the physical conditions in the innermost regions of these sources. We performed multi-frequency multi-epoch Very Long Baseline Array (VLBA) observations of the blazar CTA102 during its 2006 radio flare, the strongest ever reported for this source. These observations provide an excellent opportunity to investigate the evolution of the physical properties of blazars, especially during these flaring events Aims. We want to study the kinematic changes in the source during the strong radio outburst in April 2006 and test the assumption of a shock-shock interaction. This assumption is based on the analysis and modeling of the single dish observations of CTA102 (Paper I). Methods. In this paper we study the kinematics of CTA102 at several frequencies using VLBI observations. From the modeled jet features we derive estimates on the evolution of the physical parameters, such as the particle density and the magnetic field. Furthermore, we combine our observations during the 2006 flare with long-term VLBA monitoring of the source at 15 GHz and 43 GHz. Results. We cross-identified seven features throughout our entire multifrequency observations and find evidence of two possible recollimation shocks around 0.1   mas (deprojected 18 pc at a viewing angle ϑ = 2.6°) and 6.0   mas (deprojected 1 kpc) from the core. The 43   GHz observations reveal a feature ejected at epoch tej = 2005.9 ± 0.2, which could be connected to the 2006 April radio flare. Furthermore, this feature might be associated with the traveling component involved in the possible shock-shock interaction, which gives rise to the observed double peak structure in the single-dish light curves reported in Paper I

Requirement of RIZ1 for cancer prevention by methyl-balanced diet

The typical Western diet is not balanced in methyl nutrients that regulate the level of the methyl donor S-adenosylmethionine (SAM) and its derivative metabolite S-adenosylhomocysteine (SAH), which in turn may control the activity of certain methyltransferases. Feeding rodents with amino acid defined and methyl-imbalanced diet decreases hepatic SAM and causes liver cancers. RIZ1 (PRDM2 or KMT8) is a tumor suppressor and functions in transcriptional repression by methylating histone H3 lysine 9. Here we show that a methyl-balanced diet conferred additional survival benefits compared to a tumor-inducing methyl-imbalanced diet only in mice with wild type RIZ1 but not in mice deficient in RIZ1. While absence of RIZ1 was tumorigenic in mice fed the balanced diet, its presence did not prevent tumor formation in mice fed the imbalanced diet. Unlike most of its related enzymes, RIZ1 was upregulated by methyl-balanced diet. Methyl-balanced diet did not fully repress oncogenes such as c-Jun in the absence of RIZ1. The data identify RIZ1 as a critical target of methyl-balanced diet in cancer prevention. The molecular understanding of dietary carcinogenesis may help people make informed choices on diet, which may greatly reduce the incidence of cancer

Comparative genomic hybridization and amplotyping by arbitrarily primed PCR in stage A B-CLL

Cytogenetic analysis is useful in the diagnosis and to assess prognosis of B-cell chronic lymphocytic leukemia (B-CLL). However, successful cytogenetics by standard techniques has been hindered by the low in vitro mitotic activity of the malignant B-cell population. Fluorescence in situ hybridization (FISH) has become a useful tool, but it does not provide an overall view of the aberrations. To overcome this hurdle, two DNA-based techniques have been tested in the present study: comparative genomic hybridization (CGH) and amplotyping by arbitrarily primed PCR (AP-PCR). Comparative genomic hybridization resolution depends upon the 400-bands of the human standard karyotype. AP-PCR allows detection of allelic losses and gains in tumor cells by PCR fingerprinting, thus its resolution is at the molecular level. Both techniques were performed in 23 patients with stage A B-CLL at diagnosis. The results were compared with FISH. The sensitivity of AP-PCR was greater than CGH (62% vs. 43%). The use of CGH combined with AP-PCR allowed to detect genetic abnormalities in 79% (15/19) of patients in whom G-banding was not informative, providing a global view of the aberrations in a sole experiment. This study shows that combining these two methods with FISH, makes possible a more precise genetic characterization of patients with B-CLL

TANAMI monitoring of Centaurus A: The complex dynamics in the inner parsec of an extragalactic jet

Context. Centaurus A (Cen A) is the closest radio-loud active galactic nucleus. Very Long Baseline Interferometry (VLBI) enables us to study the spectral and kinematic behavior of the radio jet¿counterjet system on milliarcsecond scales, providing essential information for jet emission and propagation models. Aims. In the framework of the TANAMI monitoring, we investigate the kinematics and complex structure of Cen A on subparsec scales. We have been studying the evolution of the central parsec jet structure of Cen A for over 3.5 years. The proper motion analysis of individual jet components allows us to constrain jet formation and propagation and to test the proposed correlation of increased high-energy flux with jet ejection events. Cen A is an exceptional laboratory for such a detailed study because its proximity translates to unrivaled linear resolution, where one milliarcsecond corresponds to 0.018 pc. Methods. As a target of the southern-hemisphere VLBI monitoring program TANAMI, observations of Cen A are done approximately every six months at 8.4 GHz with the Australian Long Baseline Array (LBA) and associated telescopes in Antarctica, Chile, New Zealand, and South Africa, complemented by quasi-simultaneous 22.3 GHz observations. Results. The first seven epochs of high-resolution TANAMI VLBI observations at 8.4 GHz of Cen A are presented, resolving the jet on (sub-)milliarcsecond scales. They show a differential motion of the subparsec scale jet with significantly higher component speeds farther downstream where the jet becomes optically thin. We determined apparent component speeds within a range of 0.1c to 0.3c and identified long-term stable features. In combination with the jet-to-counterjet ratio, we can constrain the angle to the line of sight to theta approx 12deg-45deg. Conclusions. The high-resolution kinematics are best explained by a spine-sheath structure supported by the downstream acceleration occurring where the jet becomes optically thin. On top of the underlying, continuous flow, TANAMI observations clearly resolve individual jet features. The flow appears to be interrupted by an obstacle causing a local decrease in surface brightness and circumfluent jet behavior. We propose a jet-star interaction scenario to explain this appearance. The comparison of jet ejection times to high X-ray flux phases yields a partial overlap of the onset of the X-ray emission and increasing jet activity, but the limited data do not support a robust correlation

Future mmVLBI Research with ALMA: a European vision

Very long baseline interferometry at millimetre/submillimetre wavelengths (mmVLBI) offers the highest achievable spatial resolution at any wavelength in astronomy. The anticipated inclusion of ALMA as a phased array into a global VLBI network will bring unprecedented sensitivity and a transformational leap in capabilities for mmVLBI. Building on years of pioneering efforts in the US and Europe the ongoing ALMA Phasing Project (APP), a US-led international collaboration with MPIfR-led European contributions, is expected to deliver a beamformer and VLBI capability to ALMA by the end of 2014 (APP: Fish et al. 2013, arXiv:1309.3519). This report focuses on the future use of mmVLBI by the international users community from a European viewpoint. Firstly, it highlights the intense science interest in Europe in future mmVLBI observations as compiled from the responses to a general call to the European community for future research projects. A wide range of research is presented that includes, amongst others: - Imaging the event horizon of the black hole at the centre of the Galaxy - Testing the theory of General Relativity an/or searching for alternative theories - Studying the origin of AGN jets and jet formation - Cosmological evolution of galaxies and BHs, AGN feedback - Masers in the Milky Way (in stars and star-forming regions) - Extragalactic emission lines and astro-chemistry - Redshifted absorption lines in distant galaxies and study of the ISM and circumnuclear gas - Pulsars, neutron stars, X-ray binaries - Testing cosmology - Testing fundamental physical constant

International conference on the healthy effect of virgin olive oil

Ageing represents a great concern in developed countries because the number of people involved and the pathologies related with it, like atherosclerosis, morbus Parkinson, Alzheime's disease, vascular dementia, cognitive decline, diabetes and cancer. Epidemiological studies suggest that a Mediterranean diet (which is rich in virgin olive oil) decreases the risk of cardiovascular disease. The Mediterranean diet, rich in virgin olive oil, improves the major risk factors for cardiovascular disease, such as the lipoprotein profile, blood pressure, glucose metabolism and antithrombotic profile. Endothelial function, inflammation and oxidative stress are also positively modulated. Some of these effects are attributed to minor components of virgin olive oil. Therefore, the definition of the Mediterranean diet should include virgin olive oil. Different observational studies conducted in humans have shown that the intake of monounsaturated fat may be protective against age-related cognitive decline and Alzheimer's disease. Microconstituents from virgin olive oil are bioavailable in humans and have shown antioxidant properties and capacity to improve endothelial function. Furthermore they are also able to modify the haemostasis, showing antithrombotic properties. In countries where the populations fulfilled a typical Mediterranean diet, such as Spain, Greece and Italy, where virgin olive oil is the principal source of fat, cancer incidence rates are lower than in northern European countries. The protective effect of virgin olive oil can be most important in the first decades of life, which suggests that the dietetic benefit of virgin olive oil intake should be initiated before puberty, and maintained through life. The more recent studies consistently support that the Mediterranean diet, based in virgin olive oil, is compatible with a healthier ageing and increased longevity. However, despite the significant advances of the recent years, the final proof about the specific mechanisms and contributing role of the different components of virgin olive oil to its beneficial effects requires further investigations. © 2005 Blackwell Publishing Ltd

Colorectal carcinomas with microsatellite instability display a different pattern of target gene mutations according to large bowel site of origin

<p>Abstract</p> <p>Background</p> <p>Only a few studies have addressed the molecular pathways specifically involved in carcinogenesis of the distal colon and rectum. We aimed to identify potential differences among genetic alterations in distal colon and rectal carcinomas as compared to cancers arising elsewhere in the large bowel.</p> <p>Methods</p> <p>Constitutional and tumor DNA from a test series of 37 patients with rectal and 25 patients with sigmoid carcinomas, previously analyzed for microsatellite instability (MSI), was studied for <it>BAX</it>, <it>IGF2R</it>, <it>TGFBR2</it>, <it>MSH3</it>, and <it>MSH6 </it>microsatellite sequence alterations, <it>BRAF </it>and <it>KRAS </it>mutations, and <it>MLH1 </it>promoter methylation. The findings were then compared with those of an independent validation series consisting of 36 MSI-H carcinomas with origin from each of the large bowel regions. Immunohistochemical and germline mutation analyses of the mismatch repair system were performed when appropriate.</p> <p>Results</p> <p>In the test series, <it>IGFR2 </it>and <it>BAX </it>mutations were present in one and two out of the six distal MSI-H carcinomas, respectively, and no mutations were detected in <it>TGFBR2</it>, <it>MSH3</it>, and <it>MSH6</it>. We confirmed these findings in the validation series, with <it>TGFBR2 </it>and <it>MSH3 </it>microsatellite mutations occurring less frequently in MSI-H rectal and sigmoid carcinomas than in MSI-H colon carcinomas elsewhere (<it>P </it>= 0.00005 and <it>P </it>= 0.0000005, respectively, when considering all MSI-carcinomas of both series). No <it>MLH1 </it>promoter methylation was observed in the MSI-H rectal and sigmoid carcinomas of both series, as compared to 53% found in MSI-H carcinomas from other locations (<it>P </it>= 0.004). <it>KRAS </it>and <it>BRAF </it>mutational frequencies were 19% and 43% in proximal carcinomas and 25% and 17% in rectal/sigmoid carcinomas, respectively.</p> <p>Conclusion</p> <p>The mechanism and the pattern of genetic changes driving MSI-H carcinogenesis in distal colon and rectum appears to differ from that occurring elsewhere in the colon and further investigation is warranted both in patients with sporadic or hereditary disease.</p

A colorectal cancer susceptibility new variant at 4q26 in the Spanish population identified by genome-wide association analysis

BACKGROUND: Non-hereditary colorectal cancer (CRC) is a complex disorder resulting from the combination of genetic and non-genetic factors. Genome-wide association studies (GWAS) are useful for identifying such genetic susceptibility factors. However, the single loci so far associated with CRC only represent a fraction of the genetic risk for CRC development in the general population. Therefore, many other genetic risk variants alone and in combination must still remain to be discovered. The aim of this work was to search for genetic risk factors for CRC, by performing single-locus and two-locus GWAS in the Spanish population. RESULTS: A total of 801 controls and 500 CRC cases were included in the discovery GWAS dataset. 77 single nucleotide polymorphisms (SNP)s from single-locus and 243 SNPs from two-locus association analyses were selected for replication in 423 additional CRC cases and 1382 controls. In the meta-analysis, one SNP, rs3987 at 4q26, reached GWAS significant p-value (p = 4.02×10(-8)), and one SNP pair, rs1100508 CG and rs8111948 AA, showed a trend for two-locus association (p = 4.35×10(-11)). Additionally, our GWAS confirmed the previously reported association with CRC of five SNPs located at 3q36.2 (rs10936599), 8q24 (rs10505477), 8q24.21(rs6983267), 11q13.4 (rs3824999) and 14q22.2 (rs4444235). CONCLUSIONS: Our GWAS for CRC patients from Spain confirmed some previously reported associations for CRC and yielded a novel candidate risk SNP, located at 4q26. Epistasis analyses also yielded several novel candidate susceptibility pairs that need to be validated in independent analyses

Singular Location and Signaling Profile of Adenosine A2A-Cannabinoid CB1 Receptor Heteromers in the Dorsal Striatum

The dorsal striatum is a key node for many neurobiological processes such as motor activity, cognitive functions, and affective processes. The proper functioning of striatal neurons relies critically on metabotropic receptors. Specifically, the main adenosine and endocannabinoid receptors present in the striatum, ie, adenosine A2A receptor (A2AR) and cannabinoid CB1 receptor (CB1R), are of pivotal importance in the control of neuronal excitability. Facilitatory and inhibitory functional interactions between striatal A2AR and CB1R have been reported, and evidence supports that this cross-talk may rely, at least in part, on the formation of A2AR-CB1R heteromeric complexes. However, the specific location and properties of these heteromers have remained largely unknown. Here, by using techniques that allowed a precise visualization of the heteromers in situ in combination with sophisticated genetically-modified animal models, together with biochemical and pharmacological approaches, we provide a high resolution expression map and a detailed functional characterization of A2AR-CB1R heteromers in the dorsal striatum. Specifically, our data unveil that the A2AR-CB1R heteromer (i) is essentially absent from corticostriatal projections and striatonigral neurons, and, instead, is largely present in striatopallidal neurons, (ii) displays a striking G protein-coupled signaling profile, where co-stimulation of both receptors leads to strongly reduced downstream signaling, and (iii) undergoes an unprecedented dysfunction in Huntington’s disease, an archetypal disease that affects striatal neurons. Altogether, our findings may open a new conceptual framework to understand the role of coordinated adenosine-endocannabinoid signaling in the indirect striatal pathway, which may be relevant in motor function and neurodegenerative diseases