Ventral Striatal D2/3 Receptor Availability Is Associated with Impulsive Choice Behavior As Well As Limbic Corticostriatal Connectivity.

BACKGROUND: Low dopamine D2/3 receptor availability in the nucleus accumbens shell is associated with highly impulsive behavior in rats as measured by premature responses in a cued attentional task. However, it is unclear whether dopamine D2/3 receptor availability in the nucleus accumbens is equally linked to intolerance for delayed rewards, a related form of impulsivity. METHODS: We investigated the relationship between D2/3 receptor availability in the nucleus accumbens and impulsivity in a delay-discounting task where animals must choose between immediate, small-magnitude rewards and delayed, larger-magnitude rewards. Corticostriatal D2/3 receptor availability was measured in rats stratified for high and low impulsivity using in vivo [18F]fallypride positron emission tomography and ex vivo [3H]raclopride autoradiography. Resting-state functional connectivity in limbic corticostriatal networks was also assessed using fMRI. RESULTS: Delay-discounting task impulsivity was inversely related to D2/3 receptor availability in the nucleus accumbens core but not the dorsal striatum, with higher D2/3 binding in the nucleus accumbens shell of high-impulsive rats compared with low-impulsive rats. D2/3 receptor availability was associated with stronger connectivity between the cingulate cortex and hippocampus of high- vs low-impulsive rats. CONCLUSIONS: We conclude that delay-discounting task impulsivity is associated with low D2/3 receptor binding in the nucleus accumbens core. Thus, two related forms of waiting impulsivity-premature responding and delay intolerance in a delay-of-reward task-implicate an involvement of D2/3 receptor availability in the nucleus accumbens shell and core, respectively. This dissociation may be causal or consequential to enhanced functional connectivity of limbic brain circuitry and hold relevance for attention-deficit/hyperactivity disorder, drug addiction, and other psychiatric disorders

Limits on diffuse fluxes of high energy extraterrestrial neutrinos with the AMANDA-B10 detector

Data from the AMANDA-B10 detector taken during the austral winter of 1997 have been searched for a diffuse flux of high energy extraterrestrial muon-neutrinos, as predicted from, e.g., the sum of all active galaxies in the universe. This search yielded no excess events above those expected from the background atmospheric neutrinos, leading to upper limits on the extraterrestrial neutrino flux. For an assumed E^-2 spectrum, a 90% classical confidence level upper limit has been placed at a level E^2 Phi(E) = 8.4 x 10^-7 GeV cm^-2 s^-1 sr^-1 (for a predominant neutrino energy range 6-1000 TeV) which is the most restrictive bound placed by any neutrino detector. When specific predicted spectral forms are considered, it is found that some are excluded.Comment: Submitted to Physical Review Letter

Linagliptin Improves Insulin Sensitivity and Hepatic Steatosis in Diet-Induced Obesity

Linagliptin (tradjenta™) is a selective dipeptidyl peptidase-4 (DPP-4) inhibitor. DPP-4 inhibition attenuates insulin resistance and improves peripheral glucose utilization in humans. However, the effects of chronic DPP-4 inhibition on insulin sensitivity are not known. The effects of long-term treatment (3–4 weeks) with 3 mg/kg/day or 30 mg/kg/day linagliptin on insulin sensitivity and liver fat content were determined in diet-induced obese C57BL/6 mice. Chow-fed animals served as controls. DPP-4 activity was significantly inhibited (67–89%) by linagliptin (P<0.001). Following an oral glucose tolerance test, blood glucose concentrations (measured as area under the curve) were significantly suppressed after treatment with 3 mg/kg/day (–16.5% to –20.3%; P<0.01) or 30 mg/kg/day (–14.5% to –26.4%; P<0.05) linagliptin (both P<0.01). Liver fat content was significantly reduced by linagliptin in a dose-dependent manner (both doses P<0.001). Diet-induced obese mice treated for 4 weeks with 3 mg/kg/day or 30 mg/kg/day linagliptin had significantly improved glycated hemoglobin compared with vehicle (both P<0.001). Significant dose-dependent improvements in glucose disposal rates were observed during the steady state of the euglycemic–hyperinsulinemic clamp: 27.3 mg/kg/minute and 32.2 mg/kg/minute in the 3 mg/kg/day and 30 mg/kg/day linagliptin groups, respectively; compared with 20.9 mg/kg/minute with vehicle (P<0.001). Hepatic glucose production was significantly suppressed during the clamp: 4.7 mg/kg/minute and 2.1 mg/kg/minute in the 3 mg/kg/day and 30 mg/kg/day linagliptin groups, respectively; compared with 12.5 mg/kg/minute with vehicle (P<0.001). In addition, 30 mg/kg/day linagliptin treatment resulted in a significantly reduced number of macrophages infiltrating adipose tissue (P<0.05). Linagliptin treatment also decreased liver expression of PTP1B, SOCS3, SREBP1c, SCD-1 and FAS (P<0.05). Other tissues like muscle, heart and kidney were not significantly affected by the insulin sensitizing effect of linagliptin. Long-term linagliptin treatment reduced liver fat content in animals with diet-induced hepatic steatosis and insulin resistance, and may account for improved insulin sensitivity

Предварительное исследование применения системы спектрального регулирования для ТВС реактора ВВЭР-1000

Повышение топливных характеристик ядерных реакторов за счет применения концепции управления спектральным сдвигом (SSC) вместо традиционных методов, основанных на поглощении, является многообещающим подходом к снижению стоимости топливного цикла и увеличению использования топливных ресурсов (U, Pu). В данной работе было проведено исследование применения химического метода SSC для модели топливной сборки ВВЭР-1000 с низкообогащенным ураном, в которой контроль реактивности осуществляется путем изменения доли D2O относительно легководного замедлителя (D2O/H2O), и сравнение с поглощающими материалами, в которых содержится 600 ppm H3BO3 и 4,0 мас.% Gd2O3

Investigations in Supercritical Fluids

In recent years, supercritical fluids (SCF) have drawn substantial interest as modern solvents for chemical reactions, separations, and extractions in the area of basic research as well as in industrial processes. Especially, supercritical carbon dioxide (scCO2) is a desirable replacement for organic solvents because it is inexpensive, nontoxic, nonflammable, environmentally benign, and exhibits ease of recycling and disposal. This contribution provides for an overview of the basic physical properties of SCFs, such as density tuning, diffusivity, viscosity and interaction with fluorinated compounds. In addition, in situ NMR spectroscopy in toroid cavity autoclaves and the specialized technique of parahydrogen-induced polarization are introduced as superior and beneficial for investigating physical properties and chemical reaction in SCFs. The concept of turnover frequencies and active sites in catalysis is reviewed, while specific examples are given for homogeneous hydrogenations and hydroformylations in scCO2. The emerging field of colloid catalysis in SCFs is illustrated with the ultrafast single-phase hydrogenation of alkynes using bimetallic colloids in inverted polymer micelles as the catalyst

Recent Developments in Toroid Cavity Autoclave Engineering

A toroid cavity autoclave (TCA) is a metal pressure vessel that simultaneously functions as an NMR resonator. Since the introduction of the TCA concept, many adaptations and optimizations were put together to suit particular applications such as catalysis in supercritical fluids, rotating-frame imaging of materials, and evaluation of transport phenomena. In this article, we present recent achievements in TCA engineering that were carried out for both major fields of research with TCAs, i.e., high-pressure and imaging studies. A new modular TCA design is introduced that makes it possible to easily access all individual parts of the autoclave for maintenance and replacement. The TCA is double tuned to a high frequency for 1H and 19F resonances and a low frequency for hetero nuclei. It withstands pressures up to 400 bar at room temperature and 300 bar at temperatures up to 100°C. The autoclave sample volume is electrically separated into two compartments with only the lower compartment NMR sensitive. With the two-compartment TCA, it is possible to monitor multiple-phase systems or gas/liquid reactions in situ without sacrificing high-resolution qualities of the probe. In addition, special features are presented, such as the utilization of a second pressure line for injecting key reagents that initiate a chemical reaction or for vigorously mixing gases with a reactive solution. A newly designed resistive heater that does not introduce stray magnetic fields is also described

Homogeneous Hydrogenation in Supercritical Fluids Mediated by Colloidal Catalysts

As an intermediate form between homogeneous and heterogeneous catalysis, catalysts based on transition metal colloids have drawn a lot of attention in recent years. Mating advantages from different concepts of catalysis, they turn out to be highly active, selective, and, in addition, easily separated from other reaction components. Even though colloidal catalysts are widely used in conventional solvents, hardly anything is known about their reactivity in supercritical fluids such as supercritical carbon dioxide (scCO2). Furthermore, scCO2 is an especially attractive, non-toxic, and environmentally benign solvent for chemical reactions. When hydrogenations were conducted using polymer-supported colloidal Pd nanoparticles as catalysts in scCO2, we found turnover frequencies (TOFs) as high as 4 000 000 h-1 even at a reasonably low hydrogen pressures of 15 bar and temperatures of 50 °C. To our surprise, their reactivity turned out to be much higher than those of most other catalysts reported in the literature. The kinetics of their catalytic reactions in supercritical fluids has been investigated using in situ NMR in combination with a toroid cavity autoclave (TCA)

RIDE\u27n RIPT -- Ring Down Elimination in Rapid Imaging Pulse Trains

A new pulse sequence is introduced for compensation of acoustic ringing effects, which occur in rotating-frame images obtained with the rapid imaging pulse trains (RIPT). The new sequence (RIDE\u27n RIPT) combines features of ring down elimination (RIDE), the most common difference-spectroscopy sequence for acoustic-ringing compensation, with the advantages of RIPT for fast acquisition of magnetization profiles in B1 field gradients. For even greater time efficiency in many experiments, the two transients of RIDE\u27n RIPT are combined to a single transient in which data for the difference spectroscopy are collected sequentially. RIDE\u27n RIPT was used to record one-dimensional profiles of the proton magnetization in supercritical fluid samples of methane in carbon dioxide. The profiles showed substantial improvements over profiles obtained from standard RIPT. To withstand the high pressures required for the supercritical carbon dioxide mixtures, a toroid cavity autoclave (TCA) was used as the NMR resonator and pressure vessel. The well-defined, strong, and nonuniform B1 field of the TCA was used to resolve distances along the radial dimension

The Toroid Cavity Autoclave for High-Pressure and Variable-Temperature in situ Nuclear Magnetic Resonance Studies

The toroid cavity autoclave (TCA) is a coaxial nuclear magnetic resonance (NMR) resonator and high-pressure autoclave for in situNMR studies, which combines the advantages of a toroid NMR detector with the features of a cylindrical metal pressure vessel. It is designed to fit within the limited space of a standard NMR narrow-bore cryomagnet and allows for recording high resolution NMR spectra during chemical reactions under high pressure. Compounds that, for example, initiate a reaction can be injected into the reactor through a nonreturn valve even if the TCA is already pressurized. The TCA is heated by a resistive, coaxial heating arrangement that does not generate any stray magnetic field in the sample volume. Current pressure and temperature capabilities are 0–300 bar and room temperature to 150?°C, respectively. With standard 200 MHz 1H NMR experiments, signal resolution of 0.55 Hz and signal-to-noise ratios comparable to those of standard NMR probes were achieved. In a further development, the TCA is optimized for gas/liquid reactions in which gaseous components are vigorously mixed with the liquid to obtain maximum reaction rates. Applications to parahydrogen induced polarization are shown, in which the nuclear spin polarization patterns show pairwise addition of hydrogen in both liquid organic solvents and in supercritical CO2

Generating Long-Lasting ¹H and ¹³C Hyperpolarization in Small Molecules with Parahydrogen-Induced Polarization

Recently, Levitt and co-workers demonstrated that conserving the population of long-lasting nuclear singlet states in weak magnetic fields can lead to a preservation of nuclear spin information over times substantially longer than governed by the (high-field) spin-lattice relaxation time T1. Potential benefits of the prolonged spin information for magnetic resonance imaging and spectroscopy were pointed out, particularly when combined with the parahydrogen induced polarization (PHIP) methodology. In this contribution, we demonstrate that an increase of the effective relaxation time by a factor up to three is achieved experimentally, when molecules hyperpolarized by PHIP are kept in a weak magnetic field instead of the strong field of a typical NMR magnet. This increased lifetime of spin information makes the known PHIP phenomena more compatible with the time scales of biological processes and, thus, more attractive for future investigations