First results on radiation damage in PbWO4 crystals exposed to a 20 GeV/c proton beam

We have exposed seven full length production quality crystals of the electromagnetic calorimeter (ECAL) of the CMS detector to a 20 GeV/c proton beam at the CERN PS accelerator. The exposure was done at fluxes of 10**12 p/cm**2/h and 10**13 p/cm**2/h and integral fluences of 10**12 p/cm**2 and 10**13 p/cm**2 were reached at both rates. The light transmission of the crystals was measured after irradiation and suitable cooling time for induced radioactivity to decrease to a safe level. First results of these measurements are shown. The possible damage mechanisms are discussed and simulations based on one possible model are presented. The implications for long-term operation of CMS are discussed and it is shown that in the whole barrel and at least most of the ECAL endcap hadron damage alone - even if cumulative - should not cause the crystals to fail the CMS specification of an induced absorption coefficient muIND < 1.5 /m during the first 10 years of LHC operation.Comment: 5 pages, to be published in Proc. ICATPP Conference on Astroparticle, Particle, Space Physics, Detectors and Medical Physics Applications (Como, Italy, 6 to 10 October 2003

Molecular profiling of human endometrium and endometriosis

Endometriosis is a common hormone-dependent gynecological disease leading to severe menstrual and/or chronic pelvic pain with or without subfertility. The disease is defined by the presence of endometrium-like tissue outside the uterine cavity, primarily on the pelvic peritoneum, ovaries and infiltrating organs of the peritoneal cavity. The current tools for diagnosis and treatment of endometriosis need to be improved to ensure reliable diagnosis and effective treatment. In addition, endometriosis is associated with increased risk of ovarian cancer and, therefore, the differential diagnosis between the benign and malignant ovarian cysts is of importance. The long-term objective of the present study was to support the discovery of novel tools for diagnosis and treatment of endometriosis. This was approached by exploiting genome-wide expression analysis of endometriosis specimens. A novel expression profiling -based classification of endometriosis indicated specific subgroups of lesions partially consistent with the clinical appearance, but partially according to unknown factors. The peritoneum of women with endometriosis appeared to be altered in comparison to that of healthy control subjects, suggesting a novel aspect on the pathogenesis of the disease. The evaluation of action and metabolism of sex hormones in endometrium and endometriosis tissue indicated a novel role of androgens in regulation of the tissues. In addition, an enzyme involved in androgen and neurosteroid metabolism, hydroxysteroid (17beta) dehydrogenase 6, was found to be highly up-regulated in endometriosis tissue as compared to healthy endometrium. The enzyme may have a role in the pathogenesis of endometriosis or in the endometriosis associated pain generation. Finally, a new diagnostic biomarker, HE4, was discovered distinguishing patients with ovarian endometriotic cysts from those with malignant ovarian cancer. The information acquired in this study enables deeper understanding of endometriosis and facilitates the development of improved diagnostic tools and more specific treatments of the diseaseSiirretty Doriast

α2B-ADRENOCEPTORS IN THE REGULATION OF VASCULAR SMOOTH MUSCLE CELL CONTRACTION AND PROLIFERATION

α2-Adrenoceptors (α2-ARs) belong to the large superfamily of G protein-coupled receptors (GPCRs). They mediate important actions of the endogenous catecholamines adrenaline and noradrenaline. All three α2-AR subtypes are involved in the regulation of blood pressure and vascular tone. α2-ARs can regulate both vascular smooth muscle contraction and remodeling of the blood vessel wall, but the intracellular signaling mechanisms involved in these functions have remained largely unknown. The aim of this thesis was to investigate the involvement of the α2B-AR subtype in the regulation of the contraction and proliferation of vascular smooth muscle cells (VSMC), and to clarify the related cellular signaling mechanisms. In order to characterize the effects of α2B-AR activation on VSMC contraction and proliferation and to investigate whether these functions could be altered by drug treatment, a VSMC line stably expressing the human α2B-AR was generated by transfection of rat A7r5 cells. Characterization of the novel A7r5-α2B cell line indicated that the localization and ligand binding properties of the expressed α2B-ARs were in line with earlier studies of α2B-ARs in different host cell environments, and that the receptors had the expected pharmacological characteristics. Therefore, the generated A7r5-α2B cell line was regarded as a useful tool for investigating the functions and regulation of α2B-ARs in VSMCs. α2B-ARs were demonstrated to be capable of mediating VSMC contraction by using a functional assay measuring myosin light chain phosphorylation, which is a biochemical readout of VSMC contraction. The network of signaling pathways involved in α2B-AR-mediated contraction of A7r5 VSMCs appeared to be complex and seemed to involve many mediators, such as Gi proteins, Gβγ subunits, phospholipase C (PLC), protein kinase C (PKC) and L-type Ca2+ channels. Different screening assays, namely DNA microarray, small inhibitor compound library screening and kinase activity profiling, were used to investigate the genetic regulation and intracellular signaling mechanisms involved in α2BAR-evoked proliferation of A7r5 VSMCs. The cellular mechanisms and signal transduction pathways participating in this response appeared to be complex and included redundancy. The employed screening assays and their respective data analysis approaches were found to be useful as tools to map the activation of cellular signaling networks in a situation where the exact mechanisms still remain unknown. These screening tools were considered suitable for hypothesis generation, but additional approaches will be required for further hypothesis testing.α2-Adrenergiset reseptorit (α2-AR) ovat G-proteiinikytkentäisiä reseptoreita (GPCR). Ne aktivoituvat adrenaliinin ja noradrenaliinin vaikutuksesta ja välittävät monia tärkei- tä elimistön säätelytehtäviä. Kaikki kolme α2-AR-alatyyppiä osallistuvat verenpaineen säätelyyn. Ne voivat säädellä sekä verisuonen sileän lihaksen (VSL) supistumista että verisuonen seinämän rakenteessa tapahtuvia muutoksia. Näihin toimintoihin liittyvät solusisäiset viestintämekanismit ovat vielä suurelta osin tuntemattomia. Tämän väi- töstutkimuksen tavoitteena oli selvittää α2B-reseptorialatyypin merkitystä VSL-solujen supistumisen ja proliferaation säätelyssä ja näitä vaikutuksia välittäviä solutason vies- tintämekanismeja. Rotan A7r5-solulinjan VSL-soluihin siirrettiin ihmisen α2B-reseptoria koodittava geeni. Tämä tuotti VSL-solumallin, jonka avulla voitiin tutkia α2B-reseptorien vaikutuksia VSL-so- lujen supistumiseen ja proliferaatioon. Kehitetyn A7r5-α2B -solulinjan reseptorien sijainti ja farmakologiset ominaisuudet olivat odotuksia vastaavat. Tämän validoinnin perusteella A7r5-α2B-solulinjan todettiin soveltuvan α2B-reseptorien toiminnan tutkimiseen VSL-so- luissa. Väitöstutkimuksessa osoitettiin, että α2B-reseptorit välittävät VSL-solujen supistus- vasteita. Tätä tutkittiin mittaamalla myosiinin kevytketjujen fosforylaatiota, sillä myosiinin kevytketjujen fosforylaatio on VSL-solujen supistuksen kannalta keskeinen biokemialli- nen tapahtuma. A7r5-soluissa α2B-välitteiseen supistusvasteeseen liittyvät solunsisäiset viestintämekanismit osoittautuivat monimutkaisiksi ja niihin osallistui monia viestinvälit- täjiä, kuten Gi-proteiinit, Gβγ-alayksiköt, fosfolipaasi C, proteiinikinaasi C ja L-tyypin kal- siumkanavat. DNA-mikrosirumäärityksillä, kinaasi/fosfataasi-inhibiittorikirjaston seulon- nalla ja kinaasiaktivaatiota mittaavilla mikrosirumäärityksillä selvitettiin α2B-välitteiseen VSL-solujen proliferaatiovasteeseen liittyvää geenien ilmentymisen säätelyä ja solunsisäi- siä viestintämekanismeja. VSL-solujen proliferaatiovasteen syntyyn liittyvät mekanismit ja viestintäreitit osoittautuivat monimutkaisiksi ja osittain päällekkäisiksi. Käytetyt seulonta- menetelmät ja niihin sovellettavat analyysit todettiin käytännölliseksi lähestymistavaksi tilanteessa, jossa halutaan kartoittaa ennalta tuntemattomia solunsisäisiä viestintämeka- nismeja. Seulontamenetelmät todettiin hyödyllisiksi uusien havaintojen tuottamisessa, mutta havaintojen tuottamien hypoteesien testaamiseen tarvitaan muita, kohdennettuja menetelmiä

Radiation hardness of diamond and silicon sensors compared

The radiation hardness of silicon charged particle sensors is compared with single crystal and polycrystalline diamond sensors, both experimentally and theoretically. It is shown that for Si- and C-sensors, the NIEL hypothesis, which states that the signal loss is proportional to the Non-Ionizing Energy Loss, is a good approximation to the present data. At incident proton and neutron energies well above 0.1 GeV the radiation damage is dominated by the inelastic cross section, while at non-relativistic energies the elastic cross section prevails. The smaller inelastic nucleon-Carbon cross section and the light nuclear fragments imply that at high energies diamond is an order of magnitude more radiation hard than silicon, while at energies below 0.1 GeV the difference becomes significantly smaller.Comment: 6 pages, 4 figurs, invited talk at the Hasselt Diamond Workshop, Feb. 200

High-energy proton induced damage study of scintillation light output from PbWO4 calorimeter crystals

Eight PbWO4 crystals produced for the electromagnetic calorimeter of the CMS experiment at LHC have been irradiated in a 20 GeV/c proton beam up to fluences of 5.4 E13 p/cm2. The damage recovery in these crystals, stored in the dark at room temperature, has been followed for over a year. Comparative irradiations with 60Co photons have been performed on seven other crystals using a dose rate of 1 kGy/h. The issue whether hadrons cause a specific damage to the scintillation mechanism has been studied through light output measurements on the irradiated crystals using cosmic rays. The correlation between light output changes and light transmission changes is measured to be the same for proton-irradiated crystals and for gamma-irradiated crystals. Thus, within the precision of the measurements and for the explored range of proton fluences, no additional, hadron-specific damage to the scintillation mechanism is observed.Comment: 7 pages, 4 figure

Human epididymis protein 4 (HE4) in benign and malignant diseases

Background: Human epididymis protein 4 (HE4) is described as a useful new biomarker in ovarian cancer. As HE4 is neither tumor nor organ specific, we intensively investigated the occurrence of this protein in female and male patients with various benign and malignant diseases in order to avoid misinterpretation and to identify potential additional clinical relevance. Methods: We retrospectively investigated HE4 (ARCHITECT (R), Abbott Diagnostics, US) in the sera of 205 healthy individuals, 654 patients with benign disorders and 720 patients with cancer before initial treatment. Results: The lowest concentrations of HE4 were observed in healthy men (median 26.2 pmol/L) followed by healthy women (median 40.4 pmol/L). In benign diseases, highest HE4 concentrations were seen in both women and men with renal failure (women, median 1041 pmol/L; men, median 1368 pmol/L). In women, the highest HE4 levels in malignant diseases were observed in ovarian cancer (median 242 pmol/l), whereas the highest HE4 concentrations in men occurred in lung cancer (median 89.2 pmol/L). The area under the curve (AUC) of HE4 in women was highest in ovarian cancer and borderline tumors as compared to benign gynecological disorders (88.9%), with a sensitivity of 67.4% at 95% specificity. Also, significantly elevated concentrations of HE4 with reference to the respective group of benign diseases were observed in uterus corpus and breast cancer as well as in lung cancer for men and women. Conclusions: HE4 has the highest relevance in ovarian cancer but can be elevated in a variety of benign and malignant diseases

Properties of Pr-and BZO-doped YBCO Multilayers

AbstractMultilayers of2wt-% Pr-and4wt-% BaZrO3-doped YBa2Cu3O6+x (YBCO) were deposited by pulsed laser ablation on SrTiO3 and MgO single crystals. The structural and superconducting properties of the multilayers are presented. Multilayering was found to improve the critical temperature and structural quality of the samples on SrTiO3, but it did not change the critical current density. On MgO, the critical temperature improved slightly,but the critical current density decreased