Studies on the in vivo secretion and metabolism of the steroid hormones of the adrenal cortex

This thesis consists of publications describing experiments in which the secretion of steroid hormones by the adrenal cortex was studied. The venous effluent from the adrenal glands of several mammalian species was collected under anaesthesia. Chemical methods were developed which allow the simultaneous qualitative and quantitative analysis of most steroid hormones synthesized by the adrenal cortex. These methods were applied to blood and tissue extracts. Because of the observation (paper 1) that a large proportion of the steroids in the blood is loosely associated with blood cells, whole blood samples were extracted instead of plasma alone. The experiments have given information on the type of steroids secreted by the adrenal cortex and on factors which influence the rate at which they are secreted.One group of papers is concerned with the control of aldosterone secretion in the dog (papers 2, J and 4). A detailed study of the factors which cause a rise in aldosterone secretion following acute haemorrhage (paper 2) led to the conclusion, that acute blood loss stimulates the release of hormones from the pituitary gland and the kidney. These hormones in turn cause increased aldosterone secretion. In this respect the two organs can replace each other. In dogs which prior to the experiment had been maintained for long periods of time on either very low or very high dietary sodium intake it was usually not possible to observe the aldosterone rise after blood loss.The aldosterone stimulating substance released from the pituitary gland is in all probability ACTH. This is strongly supported by a quantitative study in which aldosterone secretion was measured in the same dog before and after hypophysectomy and during subsequent infusions of ACTH (paper 3). The increase in aldosterone secretion was found to depend on the dose of ACTH, provided aldosterone secretion was not maximally stimulated by factors not of pituitary origin. In the same experiments information was obtained on the rate at which ACTH was secreted during anaesthesia and operative stress, by comparing glucocorticoid secretion rates before hypophysectomy with those after hypophysectomy, when ACTH was infused at different ratesThe condition of the circulation before and after haemorrhage was found to be important for the ability of a dog to respond to blood loss with a rise in aldosterone secretion. The occurrence of a certain type of blood pressure waves (Mayer waves) is indicative of circulatoryA second group of papers (5 - 13) is concerned with a class of corticosteroids which has so far not been studied in a systematic and quantitative manner, mainly because they are only secreted in small quantities and methods for their estimation had not been available. The papers describe the development and adaptation of paper and gaschromatographic techniques for the purpose of a qualitative and quantitative study of these steroids.Pregnenolone, progesterone, 17αOH-progesterone, 11ßOH-progesterone and the three so called adrenal androgens androstenedione, adrenosterone and 11 SOH-androstenedione were consistently found to be present in the extracts of adrenal venous blood of dogs and young pigs in concentrations similar to or higher than those of aldosterone. Hypophysectomy caused a fall in the secretion of these steroids, similar to that of the glucocorticoids (papers 6, 8 and 9) but their secretion did not cease completely, indicating that these steroids are not only secreted by an overactive gland under conditions of stress "but also under resting conditions. In addition to the above steroids, l6αOH-progesterone was found to be secreted by the adrenal gland of the young pig). Certain experimental conditions modified the secretion of pregnenolone and 11ßOH-androstenedione in a different way from that of other steroids (paper 10). Studies of this type may eventually help to explain certain clinical signs of adrenal deficiency and overactivity which cannot fully be attributed to the lack or excess of glucocorticoids or aldosterone.The quantities of progesterone secreted by the adrenal gland of the pig (papers 5, 6 and 10) and the rat (paper 11) can be of the same order as those secreted by the ovaries of the same species (paper 12) under similar experimental conditions.A comparison between the rates at which steroids are secreted with the concentrations in which they are present in the adrenal tissue of one and the same animal provides some information on the rates of steroid synthesis in vivo (papers 9 and 10). The quantity of a given steroid present in the adrenal of a pig or dog was found to correspond to the amount secreted within 0.5 to five minutes. Pregnenolone and progesterone were exceptions to this rule. Assuming that these two steroids are the most important precursors of all the steroids secreted by the adrenal, it can be calculated, that the amounts at which they are present in the adrenal will be utilized within 1-5 minutes. Any stimulus leading to an increased secretion of adrenal steroids must therefore effect an increase in the rate at which pregnenolone is formed. In accordance with this, it was found that in the rat (paper 13) stress does not only cause a rise in the adrenal concentration of corticosterone but also of pregnenolone and progesterone.The papers 10, 14 and 15 contain information on the possible use of drugs to prevent the release of ACTH caused by anaesthesia and the operative procedures required for adrenal vein cannulation. Chlorpromazine and morphine were not able to overcome this severe stress in the rat (papers 14 and 15). In dogs anaesthetised with sodium pentobarbitone in which the left adrenal vein had been cannulated, a-ethyltryptamine had an effect on steroid secretion similar to that of hypophysectomy. However it lacked this effect in dogs anaesthetised with chloralose and in dogs which had been eviscerated(paper 10).The last paper (16) deals with the mechanism by which 17α-methylandrostenediol inhibits corticosterone production by the rat adrenal.1. Holzbauer, M. and Vogt, M. 1961. Corticosteroids in plasma and cells of adrenal venous blood. J. Physiol. 157. 137 - 156. || 2. Holzbauer, M. and Vogt, M. 1966. Investigations into the causes of the rise in aldosterone secretion during haemorrhage. Parts I and II. Phil. Trans. R. Soc. London, 250. 243 - 310. || 3. Holzbauer, M. 1964. The part played by ACTH in determining the rate of aldosterone secretion during operative stress. J. Physiol. 172. 138 - 149. || 4. Holzbauer, M. and Vogt, M. 1964. Observations on slow rhythmic blood pressure waves (Mayer waves) in the dog. J. Physiol. 172, 5 - 7P. || 5. Heap, R. B. and Holzbauer, M. 1965. Gas chromatography of androgens, progesterone and progesterone derivatives in adrenal venous blood of pigs and dogs. J. Physiol. 183. 11 P. || 6. Heap, R. B., Holzbauer, M. and Newport, H. M. 1966. Adrenal secretion rates of C-19 and C-21 steroids before and after hypophysectomy in the pig and the dog. J. Endocr. 56. 159 - 176. || 7. Holzbauer, M. and Newport, H. M. 1967. Evidence for the presence of l6α-hydroxypregn-4-ene-3,2C-dione in adrenal venous blood of young pigs. J. Physiol. 191. 691 - 697. || 8. Holzbauer, M. and Newport, H. M. 1968. Secretion of 5P~ hydroxypregn-5-en-20-one (pregnenolone) by the adrenal gland. Nature, 217, 967 - 968. || 9. Holzbauer, M. and Newport, H. M. 1968. Quantitative estimation of 17α-hydroxypregn-4-ene-3, 20-dione (l7αOH-progesterone) in adrenal venous blood and adrenal glands. J. Physiol. 198, 91 - 102. || 10. Holzbauer, M. and Newport, H. M. 1969. Adrenal secretion rates and adrenal tissue concentrations of pregnenolone, progesterone, 11ßOH-androstenedione and some other steroids in young pigs and dogs. J. Physiol. 200, 821 - 848. || 11. Holzbauer, M., Newport, H. K., Birmingham, M. K. and Traikov, H. 1969. Secretion of pregn-4-ene-3,20-dione (progesterone) in vivo by the adrenal gland of the rat. Nature, 221. 572 - 573. || 12. Fajer, A. B. and Holzbauer, M. 1968. Pregnenolone, progesterone and 20-dihydroprogesterone in rat ovarian blood and ovaries during the oestrous cycle. J. Physiol. 196. 99 - 101P. || 13. Holzbauer, M, and Newport, H. M. 1967. The effect of stress on the concentration of 3ß-hydroxypregn-5-en-20-one (pregnenolone) and pregn-4-ene-3,20-dione (progesterone) in the adrenal gland of the rat. J. Physiol. 193. 131 - 140. || 14. Holzbauer, M. and Vogt, M. 1954. The action of chlorpromazine on diencephalic sympathetic activity and on the release of adrenocorticotrophic hormone. Br. J. Pharmac. Chemother. 2, 402 - 407. || 15. Holzbauer, M. and Vogt, M. 1958. The release of corticotrophin during severe stress in the rat treated with pentobarbitone and morphine. Acta Endocrinologica 29. 231 - 237. || 16. Rembeisa, H., Holzbauer, M., Young, P. C. M., Birmingham, M, K. and Saffran, M, 1967. Metabolism of 17a-methylandrostenediol and 17ß-methyltestosterone by the rat adrenal gland in vitro. Endocrinology, 81, 1278 - 128

The signature of the first stars in atomic hydrogen at redshift 20

Dark and baryonic matter moved at different velocities in the early Universe, which strongly suppressed star formation in some regions. This was estimated to imprint a large-scale fluctuation signal of about 2 mK in the 21-cm spectral line of atomic hydrogen associated with stars at a redshift of 20, although this estimate ignored the critical contribution of gas heating due to X-rays and major enhancements of the suppression. A large velocity difference reduces the abundance of halos and requires the first stars to form in halos of about a million solar masses, substantially greater than previously expected. Here we report a simulation of the distribution of the first stars at z=20 (cosmic age of ~180 Myr), incorporating all these ingredients within a 400 Mpc box. We find that the 21-cm signature of these stars is an enhanced (10 mK) fluctuation signal on the 100-Mpc scale, characterized by a flat power spectrum with prominent baryon acoustic oscillations. The required sensitivity to see this signal is achievable with an integration time of a thousand hours with an instrument like the Murchison Wide-field Array or the Low Frequency Array but designed to operate in the range of 50-100 MHz.Comment: 27 pages, 5 figures, close (but not exact) match to accepted version. Basic results unchanged from first submitted version, but justification strengthened, title and abstract modified, and substantial Supplementary Material added. Originally first submitted for publication on Oct. 12, 201

Installation, commissioning, and testing of the HB650 CM at PIP2IT

The Proton Improvement Plan-II (PIP-II) is a major upgrade to the Fermilab accelerator complex, featuring a new 800-MeV Superconducting Radio-Frequency (SRF) linear accelerator (LINAC) powering the accelerator complex to provide the world's most intense high-energy neutrino beam. This paper describes the conversion of the PIP-II Injector Test Facility (PIP2IT) cryogenic system into a test stand for PIP-II High-Beta 650 MHz (HB650) cryomodules at Fermilab's Cryomodule Test Facility (CMTF). A description of the associated mechanical, electrical, and controls modifications necessary for testing HB650 cryomodules are provided. The cooldown and warmup requirements, procedures and associated controls logic is described.Comment: 2023 Cryogenic Engineering Conference and International Cryogenic Materials Conference (CEC/ICMC

Journal Staff

We present the first measurements of the differential cross section d sigma/dp(T)(gamma) for the production of an isolated photon in association with at least two b-quark jets. The measurements consider photons with rapidities vertical bar y(gamma)vertical bar < 1.0 and transverse momenta 30 < p(T)(gamma) < 200 GeV. The b-quark jets are required to have p(T)(jet) > 15 GeVand vertical bar y(jet)vertical bar < 1.5. The ratio of differential production cross sections for gamma + 2 b-jets to gamma + b-jet as a function of p(T)(gamma) is also presented. The results are based on the proton-antiproton collision data at root s = 1.96 TeV collected with the D0 detector at the Fermilab Tevatron Collider. The measured cross sections and their ratios are compared to the next- to- leading order perturbative QCD calculations as well as predictions based on the k(T)- factorization approach and those from the sherpa and pythia Monte Carlo event generators

Single hadron response measurement and calorimeter jet energy scale uncertainty with the ATLAS detector at the LHC

The uncertainty on the calorimeter energy response to jets of particles is derived for the ATLAS experiment at the Large Hadron Collider (LHC). First, the calorimeter response to single isolated charged hadrons is measured and compared to the Monte Carlo simulation using proton-proton collisions at centre-of-mass energies of sqrt(s) = 900 GeV and 7 TeV collected during 2009 and 2010. Then, using the decay of K_s and Lambda particles, the calorimeter response to specific types of particles (positively and negatively charged pions, protons, and anti-protons) is measured and compared to the Monte Carlo predictions. Finally, the jet energy scale uncertainty is determined by propagating the response uncertainty for single charged and neutral particles to jets. The response uncertainty is 2-5% for central isolated hadrons and 1-3% for the final calorimeter jet energy scale.Comment: 24 pages plus author list (36 pages total), 23 figures, 1 table, submitted to European Physical Journal

Measurement of the top quark mass using the matrix element technique in dilepton final states

We present a measurement of the top quark mass in pp¯ collisions at a center-of-mass energy of 1.96 TeV at the Fermilab Tevatron collider. The data were collected by the D0 experiment corresponding to an integrated luminosity of 9.7  fb−1. The matrix element technique is applied to tt¯ events in the final state containing leptons (electrons or muons) with high transverse momenta and at least two jets. The calibration of the jet energy scale determined in the lepton+jets final state of tt¯ decays is applied to jet energies. This correction provides a substantial reduction in systematic uncertainties. We obtain a top quark mass of mt=173.93±1.84  GeV

Standalone vertex finding in the ATLAS muon spectrometer

A dedicated reconstruction algorithm to find decay vertices in the ATLAS muon spectrometer is presented. The algorithm searches the region just upstream of or inside the muon spectrometer volume for multi-particle vertices that originate from the decay of particles with long decay paths. The performance of the algorithm is evaluated using both a sample of simulated Higgs boson events, in which the Higgs boson decays to long-lived neutral particles that in turn decay to bbar b final states, and pp collision data at √s = 7 TeV collected with the ATLAS detector at the LHC during 2011

Measurements of Higgs boson production and couplings in diboson final states with the ATLAS detector at the LHC

Measurements are presented of production properties and couplings of the recently discovered Higgs boson using the decays into boson pairs, H →γ γ, H → Z Z∗ →4l and H →W W∗ →lνlν. The results are based on the complete pp collision data sample recorded by the ATLAS experiment at the CERN Large Hadron Collider at centre-of-mass energies of √s = 7 TeV and √s = 8 TeV, corresponding to an integrated luminosity of about 25 fb−1. Evidence for Higgs boson production through vector-boson fusion is reported. Results of combined fits probing Higgs boson couplings to fermions and bosons, as well as anomalous contributions to loop-induced production and decay modes, are presented. All measurements are consistent with expectations for the Standard Model Higgs boson