Incretin-based therapy: a powerful and promising weapon in the treatment of type 2 diabetes mellitus

Type 2 diabetes mellitus (T2DM) is a progressive multisystemic disease that increases significantly cardiovascular morbidity and mortality. It is associated with obesity, insulin resistance, beta-cell dysfunction, and hyperglucagonemia, the combination of which typically leads to hyperglycemia. Incretin-based treatment modalities, and in particular glucagon-like peptide 1 (GLP-1) receptor agonists, are able to successfully counteract several of the underlying pathophysiological abnormalities of T2DM. The pancreatic effects of GLP-1 receptor agonists include glucose-lowering effects by stimulating insulin secretion and inhibiting glucagon release in a strictly glucose-dependent manner, increased beta-cell proliferation, and decreased beta-cell apoptosis. GLP-1 receptors are widely expressed throughout human body; thus, GLP-1-based therapies exert pleiotropic and multisystemic effects that extend far beyond pancreatic islets. A large body of experimental and clinical data have suggested a considerable protective role of GLP-1 analogs in the cardiovascular system (decreased blood pressure, improved endothelial and myocardial function, functional recovery of failing and ischemic heart, arterial vasodilatation), kidneys (increased diuresis and natriuresis), gastrointestinal tract (delayed gastric emptying, reduced gastric acid secretion), and central nervous system (appetite suppression, neuroprotective properties). The pharmacologic use of GLP-1 receptor agonists has been shown to reduce bodyweight and systolic blood pressure, and significantly improve glycemic control and lipid profile. Interestingly, weight reduction induced by GLP-1 analogs reflects mainly loss of abdominal visceral fat. The critical issue of whether the emerging positive cardiometabolic effects of GLP-1 analogs can be translated into better clinical outcomes for diabetic patients in terms of long-term hard endpoints, such as cardiovascular morbidity and mortality, remains to be elucidated with prospective, large-scale clinical trials

Search for resonances decaying into photon pairs in 139 fb−1 of pp collisions at √s = 13 TeV with the ATLAS detector

Searches for new resonances in the diphoton final state, with spin 0 as predicted by theories with an extended Higgs sector and with spin 2 using a warped extra-dimension benchmark model, are presented using 139 fb−1 of √s = 13 TeV pp collision data collected by the ATLAS experiment at the LHC. No significant deviation from the Standard Model is observed and upper limits are placed on the production cross-section times branching ratio to two photons as a function of the resonance mass

Radial-pulse propagation and impedance characteristics of optically shuttered channel intensifier tubes

Electrically gated proximity-focused channel intensifier tubes are often used as optical shutters. Optimum nanosecond shuttering requires both understanding the electrical pulse propagation across the device structure and proper impedance matching. A distributed-transmission-line model is developed that describes analytically the voltage- and current-wave propagation characteristics as functions of time for any point on the surface. The optical gain's spatial uniformity and shutter-open times are shown to depend on the electrical pulse width and amplitude, and on the applied bias. The driving-point impedance is derived from the model and is expressed as a function of an infinite sum of terms in the complex frequency. The synthesis in terms of lumped-constant network elements is realized in first- and second-Foster equivalent circuits. Experimental impedance data are compared with the model's predictions and deviations from the ideal model are discussed

FPS-vidicon television camras for ultrafast-scan data acquisition

Two ultrafast-scan (<8 ms/field) television (TV) camera prototypes have been developed for closed-circuit data-acquisition applications. The line and field rates are quasi-continuously adjustable. The number of lines, the integration duty cycle, and the scan direction are among the other adjustable parameters. Typical resolution at the fastest scan rate is >500 TV lines per picture height with a corresponding dynamic range (to light input) of more than 100. The cameras use the unique properties of FPS vidicons and specially designed electronics to achieve their performance levels and versatility. The advantages and disadvantages of FPS vidicons and of antimony trisulfide and silicon target materials in such applications are discussed in detail. All of the electronics circuits are discussed. The sweep generator designs are treated at length because they are the key to the cameras' versatility. Emphasis is placed on remotely controllable analog and digital sweep generators. The latter is a complete CAMAC-compatible subsystem containing a 16-function master arithmetic logic unit. Pulsed and cw methods of obtaining transfer characteristics are described and compared. The effects of generation rates, tube types, and target types on the resolution, determined from contrast-transfer-function curves, are discussed. Several applications are described, including neutron TV pinhole, TREAT, and barium-release experiments

Image shutters: gated proximity-focused microchannel-plate (MCP) wafer tubes vs gated silicon intensified target (SIT) vidicons

The imaging characteristics of two fast image shutters used for recording the spatial and temporal evolution of transient optical events in the nanosecond range have been studied. Emphasis is on the comparative performances of each shutter type under similar conditions. Response data, including gating speed, gain, dynamic range, shuttering efficiency, and resolution for 18 and 25-mm-diam proximity-focused microchannel-plate (MCP) intensifiers are compared with similar data for a prototype electrostatically-focused 25-mm-diam gated silicon-intensified-target (SIT) vidicon currently under development for Los Alamos National Laboratory. Several key parameters critical to optical gating speed have been varied in both tube types in order to determine the optimum performance attainable from each design. These include conductive substrate material and thickness used to reduce photocathode resistivity, spacing between gating electrodes to minimize inter-electrode capacitance, the use of conductive grids on the photocathode substrate to permit rapid propagation of the electrical gate pulse to all areas of the photocathode, and different package geometries to provide a more effective interface with external biasing and gating circuitry. For comparable spatial resolution, most 18-mm-diam MCPs require gate times > 2.5 ns while the fastest SIT has demonstrated sub-nanosecond optical gates as short as approx. 400 +- 50 ps for full shuttering of the 25-mm-diam input window

Remote temperature-measurement instrumentation for a heated rotating turbine disk

Thermographic-phosphor (TP) remote temperature sensors were installed on a turbine disk and subjected to thermal and centrifugal stresses in a spin-pit test. The sensors were placed at three different radii on the disk, which was run at 6600, 9330, 11400, and 13200 rpm at nominal temperatures of ambient, 300) degree)F, 600)degree)F, 900)degree)F, and 1250)degree)F (149)degree)C, 316)degree)C, 482)degree)C, and 677)degree)C, respectively). The paper gives details of the TP temperature-measurement method, phosphor bonding to the disk, calibration, optical-system design, and electronics instrumentation. The temperatures measured by the TP sensors were compared with those measured by thermocouples mounted on the disk. A number of the thermocouples behaved erratically after we operated the disk at 677)degree)C for an extended period. Nevertheless, for those cases where they could be compared with confidence, the agreement between the TP sensors and the thermocouples was good. 6 refs., 7 figs., 4 tabs

Application of linear accelerator technology to the detection of trace amounts of transuranics in waste barrels

Electron linear accelerators (linacs), as sources of photons and neutrons, can produce a significant number of fissions in transuranic isotopes contained in large barrels of waste material. Both photons and thermal neutrons have been used to detect about 1 mg of plutonium in 105-kg matrices. A sequential interrogation with neutrons and photons, easily possible with linacs, can show both fertile and fissile constituents among the heavy-mass isotopes. The advantages of linacs in solving existing assay problems include: (1) high available beam current; (2) variable beam current, beam energy, pulse width, and pulse repetition frequency; and (3) beam-scanning ability. They also are compatible with passive assay instruments. Their versatility makes it likely that they will remain useful as assay technology advances