METABOLIC EFFECTS OF SULFONYLUREAS IN NORMAL MEN and IN VARIOUS TYPES OF DIABETIC PATIENTS

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73037/1/j.1749-6632.1957.tb54592.x.pd

Improving the sensitivity of future GW observatories in the 1-10 Hz band: Newtonian and seismic noise

The next generation gravitational wave interferometric detectors will likely be underground detectors to extend the GW detection frequency band to frequencies below the Newtonian noise limit. Newtonian noise originates from the continuous motion of the Earth’s crust driven by human activity, tidal stresses and seismic motion, and from mass density fluctuations in the atmosphere. It is calculated that on Earth’s surface, on a typical day, it will exceed the expected GW signals at frequencies below 10 Hz. The noise will decrease underground by an unknown amount. It is important to investigate and to quantify this expected reduction and its effect on the sensitivity of future detectors, to plan for further improvement strategies. We report about some of these aspects. Analytical models can be used in the simplest scenarios to get a better qualitative and semi-quantitative understanding. As more complete modeling can be done numerically, we will discuss also some results obtained with a finite-element-based modeling tool. The method is verified by comparing its results with the results of analytic calculations for surface detectors. A key point about noise models is their initial parameters and conditions, which require detailed information about seismic motion in a real scenario. We will describe an effort to characterize the seismic activity at the Homestake mine which is currently in progress. This activity is specifically aimed to provide informations and to explore the site as a possible candidate for an underground observatory. Although the only compelling reason to put the interferometer underground is to reduce the Newtonian noise, we expect that the more stable underground environment will have a more general positive impact on the sensitivity.We will end this report with some considerations about seismic and suspension noise

Identification of a Novel Pseudo-Natural Product Type IV IDO1 Inhibitor Chemotype

Natural product (NP)-inspired design principles provide invaluable guidance for bioactive compound discovery. Pseudo-natural products (PNPs) are de novo combinations of NP fragments to target biologically relevant chemical space not covered by NPs. We describe the design and synthesis of apoxidoles, a novel pseudo-NP class, whereby indole- and tetrahydropyridine fragments are linked in monopodal connectivity not found in nature. Apoxidoles are efficiently accessible by an enantioselective [4+2] annulation reaction. Biological evaluation revealed that apoxidoles define a new potent type IV inhibitor chemotype of indoleamine 2,3-dioxygenase 1 (IDO1), a heme-containing enzyme considered a target for the treatment of neurodegeneration, autoimmunity and cancer. Apoxidoles target apo-IDO1, prevent heme binding and induce unique amino acid positioning as revealed by crystal structure analysis. Novel type IV apo-IDO1 inhibitors are in high demand, and apoxidoles may provide new opportunities for chemical biology and medicinal chemistry research

A double-sided, shield-less stave prototype for the ATLAS upgrade strip tracker for the high luminosity LHC

A detailed description of the integration structures for the barrel region of the silicon strips tracker of the ATLAS Phase-II upgrade for the upgrade of the Large Hadron Collider, the so-called High Luminosity LHC (HL-LHC), is presented. This paper focuses on one of the latest demonstrator prototypes recently assembled, with numerous unique features. It consists of a shortened, shield-less, and double sided stave, with two candidate power distributions implemented. Thermal and electrical performances of the prototype are presented, as well as a description of the assembly procedures and tools

Sensitivity Studies for Third-Generation Gravitational Wave Observatories

Advanced gravitational wave detectors, currently under construction, are expected to directly observe gravitational wave signals of astrophysical origin. The Einstein Telescope, a third-generation gravitational wave detector, has been proposed in order to fully open up the emerging field of gravitational wave astronomy. In this article we describe sensitivity models for the Einstein Telescope and investigate potential limits imposed by fundamental noise sources. A special focus is set on evaluating the frequency band below 10Hz where a complex mixture of seismic, gravity gradient, suspension thermal and radiation pressure noise dominates. We develop the most accurate sensitivity model, referred to as ET-D, for a third-generation detector so far, including the most relevant fundamental noise contributions.Comment: 13 pages, 7 picture

Scientific Potential of Einstein Telescope

Einstein gravitational-wave Telescope (ET) is a design study funded by the European Commission to explore the technological challenges of and scientific benefits from building a third generation gravitational wave detector. The three-year study, which concluded earlier this year, has formulated the conceptual design of an observatory that can support the implementation of new technology for the next two to three decades. The goal of this talk is to introduce the audience to the overall aims and objectives of the project and to enumerate ET's potential to influence our understanding of fundamental physics, astrophysics and cosmology.Comment: Conforms to conference proceedings, several author names correcte