AGN counts at 15um. XMM observations of the ELAIS-S1-5 sample

Context: The counts of galaxies and AGN in the mid infra-red (MIR) bands are important instruments for studying their cosmological evolution. However, the classic spectral line ratios techniques can become misleading when trying to properly separate AGN from starbursts or even from apparently normal galaxies. Aims: We use X-ray band observations to discriminate AGN activity in previously classified MIR-selected starburst galaxies and to derive updated AGN1 and (Compton thin) AGN2 counts at 15 um. Methods: XMM observations of the ELAIS-S1 15um sample down to flux limits ~2x10^-15 erg cm^-2 s^-1 (2-10 keV band) were used. We classified as AGN all those MIR sources with a unabsorbed 2-10 keV X-ray luminosity higher that ~10^42 erg/s. Results: We find that at least about 13(+/-6) per cent of the previously classified starburst galaxies harbor an AGN. According to these figures, we provide an updated estimate of the counts of AGN1 and (Compton thin) AGN2 at 15 um. It turns out that at least 24% of the extragalactic sources brighter than 0.6 my at 15 um are AGN (~13% contribution to the extragalactic background produced at fluxes brighter than 0.6 mJy).Comment: Accepted for publication on A&

Caveolin-1 as a promoter of tumour spreading: when, how, where and why.

Caveolae are non-clathrin invaginations of the plasma membrane in most cell types; they are involved in signalling functions and molecule trafficking, thus modulating several biological functions, including cell growth, apoptosis and angiogenesis. The major structural protein in caveolae is caveolin-1, which is known to act as a key regulator in cancer onset and progression through its role as a tumour suppressor. Caveolin-1 can also promote cell proliferation, survival and metastasis as well as chemo- and radioresistance. Here, we discuss recent findings and novel concepts that support a role for caveolin-1 in cancer development and its distant spreading. We also address the potential application of caveolin-1 in tumour therapy and diagnosis

The XMM-Newton survey of the ELAIS-S1 field II: optical identifications and multiwavelength catalogue of X-ray sources

We present optical identifications and a multi-band catalogue of a sample of 478 X-ray sources in the XMM and Chandra surveys of the central 0.6 deg^2 of the ELAIS-S1 field. The optical/infrared counterpart of each X-ray source was identified using R and IRAC 3.6 um bands. This method was complemented by the precise positions obtained through Chandra observations. Approximately 94% of the counterparts are detected in the R band, while the remaining are blank fields in the optical down to R~24.5, but have a near-infrared counterpart detected by IRAC within 6 arcsec from the XMM centroid. The multi-band catalogue contains photometry in ten photometric bands (B to the MIPS 24 um). We determined redshift and classification for 237 sources (~50% of the sample) brighter than R=24. We classified 47% of the sources with spectroscopic redshift as broad-line active galactic nuclei (BL AGNs) with z=0.1-3.5, while sources without broad-lines are about 46% of the spectroscopic sample and are found up to z=2.6. We identified 11 type 2 QSOs among the sources with X/O>8, with z=0.9-2.6, high 2-10 keV luminosity (log(L2-10keV)>=43.8 erg/s) and hard X-ray colors suggesting large absorbing columns at the rest frame (logN_H up to 23.6 cm^-2). BL AGNs show on average blue optical-to-near-infrared colors, softer X-ray colors and X-ray-to-optical colors typical of optically selected AGNs. Conversely, narrow-line sources show redder optical colors, harder X-ray flux ratio and span a wider range of X-ray-to-optical colors. On average the SEDs of high-luminosity BL AGNs resemble the power-law typical of unobscured AGNs. The SEDs of NOT BL AGNs are dominated by the galaxy emission in the optical/near-infrared, and show a rise in the mid-infrared which suggests the presence of an obscured active nucleus.Comment: 15 pages, A&A accepted, affiliations correcte

Fenntartható fluoros kémia = Sustainable fluorous chemistry

(1) A „zöldebb” fluoros kémia kialakítása érdekében számos trifluormetil-csoportban gazdag reagens hatékony szintézisét dolgoztuk ki, melyek könnyen hozzáférhető szerves fluorvegyületek hasznosítására és várhatóan nagyobb környezeti lebomlási készségére hívják fel a figyelmet. (2) Eljárásokat dolgoztunk ki 3-perfluoralkil-propanol és 3-perfluoralkil-propén típusú intermedierek előállítására, illetve a köztitermékként megjelenő ún. jódhidrinek sokoldalú preparatív átalakítására. (3) Új típusú fluoros ionos folyadékokat, imidazólium-sókat és más intermediereket állítottunk elő. (4) Orosz fejlesztésű kompozit anyagokat (FUKM, FUKM-M és FUKM-MT) kémiai reagensként, illetve átmenetifém katalizátor (Pd/FUKM) hordozóként alkalmaztunk. (5) Tanulmányoztuk a Hiyama- és a Heck-kapcsolási reakciók mechanizmusát és szintetikus alkalmazhatóságát. (6) CF3I reagnest S-alkilezőszerként alkalmaztuk (7) Prof. Bühlmann al együttműködve fluoros ionofórokat és elektrokémiai szenzorokat készítettünk. (8) Azonosítottuk egy új potenciális fluorátvivő reagens molekulaszerkezeti feltételeit, melynek segítségével lehetőségünk nyílik a fluoros kémiából (fluortartalmú modulok) a fluorkémiába (szén-fluor kötesek kialakítása) átlépnünk. Ez lehetőséget ad a gyógyszerkémia számára fontos egy, kettő, vagy három fluoratomot tartalmazó vegyületek hatékony előállításához. Több közlemény csak a kövtekező évben fog megjelenni, kérem az értékelésnél ezt vegyék figyelembe. | (1) For Greener Fluorous Chemistry we developed the synthesis of several reagents from easily accessible precursor, reach in CF3-goups, which expected to have less impact and shorter environmental half-lives. (2) Novel methods for the synthesis of 3-perfluoroalkyl-propanols and –propenes were disclosed along with the uses of their synthetic intermediates. (3) New types of fluorous ionic liquids were synthesised based on imidazolium-salts. (4) Carbon-fluorinated carbon composite materials of Russian origin were applied as chemical reagents and transition metal catalyst support material (e.g. Pd/FUKM) . (5) Hiyama- and Heck-reactions with fluorous substrates were studied for a synthetic and mechanistic point of view. (6) Trifluoroiodomethane was used for improved S-alkylating processes. (7) Fluorous ionophores and electrochemical sensors were designed for the first time in co-operation with Prof. Bühlmann. (8) The structural requirements for a potential new fluorine-transfer reagent were identified and a Patentable process designed. This will allow the introduction of one, two or three fluorine atoms into target pharmaceutical molecules, and allow a shift from the fluorous to the fluorine chemistry (i.e. from F-building blocks to create C-F bonds). Please consider that some more publications are expected to appear only in the next year

Compton Thick AGN in the XMM-COSMOS survey

Heavily obscured, Compton Thick (CT, NH>10^24 cm^-2) AGN may represent an important phase in AGN/galaxy co-evolution and are expected to provide a significant contribution to the cosmic X-ray background (CXB). Through direct X-ray spectra analysis, we selected 39 heavily obscured AGN (NH>3x10^23 cm^-2) in the 2 deg^2 XMM-COSMOS survey. After selecting CT AGN based on the fit of a simple absorbed two power law model to the XMM data, the presence of CT AGN was confirmed in 80% of the sources using deeper Chandra data and more complex models. The final sample of CT AGN comprises 10 sources spanning a large range of redshift and luminosity. We collected the multi-wavelength information available for all these sources, in order to study the distribution of SMBH and host properties, such as BH mass (M_BH), Eddington ratio (\lambda_Edd), stellar mass (M*), specific star formation rate (sSFR) in comparison with a sample of unobscured AGN. We find that highly obscured sources tend to have significantly smaller M_BH and higher \lambda_edd with respect to unobscured ones, while a weaker evolution in M* is observed. The sSFR of highly obscured sources is consistent with the one observed in the main sequence of star forming galaxies, at all redshift. We also present optical spectra, spectral energy distribution (SED) and morphology for the sample of 10 CT AGN: all the available optical spectra are dominated by the stellar component of the host galaxy, and a highly obscured torus component is needed in the SED of the CT sources. Exploiting the high resolution Hubble-ACS images available, we conclude that these highly obscured sources have a significantly larger merger fraction with respect to other X-ray selected samples of AGN. Finally we discuss implications in the context of AGN/galaxy co-evolutionary models, and compare our results with the predictions of CXB synthesis models.Comment: Revised version after referee comments. Accepted for publication in Astronomy & Astrophysics on 25 November 2014. 23 pages, 2 tables, 16 figure

Improved renal survival in Japanese children with IgA nephropathy

Since the beginning of the 1990s, Japanese medical practitioners have extensively prescribed angiotensin-converting enzyme (ACE) inhibitors for children with mild IgA nephropathy (IgA-N) and steriods for those with severe IgA-N. We have performed a retrospective cohort study to clarify whether the long-term outcome has improved in Japanese children with IgA-N. Renal survival was defined as the time from onset to end-stage renal disease (ESRD). We divided the study period into two time periods based on the occurrence of the initial renal biopsy:1976–1989 and 1990–2004. Actuarial survivals were calculated by Kaplan–Meier method, and comparisons were made with the logrank test. The Cox proportional hazard model was used for multivariate analysis. Between 1976 and 2004, 500 children were diagnosed as having IgA-N in our hospitals. The actuarial renal survival from the time of apparent disease onset was 96.4% at 10 years, 84.5% at 15 years and 73.9% at 20 years. Renal survival in the 1990–2004 period was significantly better than that in 1976–1989 (p = 0.008), and a marked improvement in renal survival in patients with severe IgA-N was also observed (p = 0.0003). Multivariate analysis indicated that diagnosis year was a significant factor for ESRD-free survival independently of baseline characteristics. The results of this study show that there has been an improvement in terms of renal survival in Japanese children with IgA-N

AT7519, a Novel Small Molecule Multi-Cyclin Dependent Kinase Inhibitor, Induces Apoptosis in Multiple Myeloma VIA GSK3 beta

Dysregulated cell cycling is a universal hallmark of cancer and is often mediated by abnormal activation of cyclin-dependent kinases (CDKs) and their cyclin partners. Overexpression of individual complexes are reported in multiple myeloma (MM), making them attractive therapeutic targets. In this study, we investigate the preclinical activity of a novel small-molecule multi-CDK inhibitor, AT7519, in MM. We show the anti-MM activity of AT7519 displaying potent cytotoxicity and apoptosis; associated with in vivo tumor growth inhibition and prolonged survival. At the molecular level, AT7519 inhibited RNA polymerase II (RNA pol II) phosphorylation, a CDK9, 7 substrate, associated with decreased RNA synthesis confirmed by [(3)H] Uridine incorporation. In addition, AT7519 inhibited glycogen synthase kinase 3beta (GSK-3beta) phosphorylation; conversely pretreatment with a selective GSK-3 inhibitor and shRNA GSK-3beta knockdown restored MM survival, suggesting the involvement of GSK-3beta in AT7519-induced apoptosis. GSK-3beta activation was independent of RNA pol II dephosphorylation confirmed by alpha-amanitin, a specific RNA pol II inihibitor, showing potent inhibition of RNA pol II phosphorylation without corresponding effects on GSK-3beta phosphorylation. These results offer new insights into the crucial, yet controversial role of GSK-3beta in MM and show significant anti-MM activity of AT7519, providing the rationale for its clinical evaluation in MM

Lupus anticoagulant identifies two distinct groups of patients with different antibody patterns

Background: Whether antibodies directed to β2-Glycoprotein I (aβ2GPI) are responsible for LA activity is not well defined. However, in the absence of such antibodies the molecule responsible for LA phenomenon is unknown. Objective: The aim of this study was the biochemical identification of the target antigen epitope of aPL responsible of LA activity in the absence of aβ2GPI antibodies together with the biological and clinical characteristics of these patients in comparison with classical triple positive patients. Patients/methods: A comparison of patients with LA without (LA+/aβ2GPI−) and those with (LA+/aβ2GPI+) associated aβ2GPI antibodies was performed. Size exclusion chromatography and analytical chromatography were used to identify the molecule with LA activity in patients LA+/aβ2GPI-. Results and conclusions: Analytical size-exclusion chromatography revealed a peak of 996Kd with LA activity perfectly overlapping that of IgM anti phosphatidylserine/prothrombin (aPS/PT) antibodies. Similarly, all the 25 LA+/aβ2GPI− patients were positive for aPS/PT antibodies. LA+/aβ2GPI− compared to 33 LA+/aβ2GPI+ patients turned out to be significantly older, with a lower rate of previous thromboembolic events and a weaker LA activity. Search for aPS/PT and aβ2GPI antibodies in patients with LA is useful to identify two subgroups of LA at different risk of thromboembolic event