Involvement of Glutamate NMDA Receptors in the Acute, Long-Term, and Conditioned Effects of Amphetamine on Rat 50kHz Ultrasonic Vocalizations

BACKGROUND: Rats emit 50kHz ultrasonic vocalizations (USVs) in response to either natural or pharmacological pleasurable stimuli, and these USVs have emerged as a new behavioral measure for investigating the motivational properties of drugs. Earlier studies have indicated that activation of the dopaminergic system is critically involved in 50kHz USV emissions. However, evidence also exists that non-dopaminergic neurotransmitters participate in this behavioral response. METHODS:To ascertain whether glutamate transmission plays a role in 50kHz USV emissions stimulated by amphetamine, rats received five amphetamine (1-2mg/kg, i.p.) administrations on alternate days in a test cage, either alone or combined with the glutamate N-methyl-D-aspartate receptor antagonist MK-801 (0.1-0.5mg/kg, i.p.). Seven days after treatment discontinuation, rats were re-exposed to the test cage to assess drug conditioning, and afterwards received a drug challenge. USVs and locomotor activity were evaluated, along with immunofluorescence for Zif-268 in various brain regions and spontaneous alternation in a Y maze. RESULTS:Amphetamine-treated rats displayed higher 50kHz USV emissions and locomotor activity than vehicle-treated rats, and emitted conditioned vocalizations on test cage re-exposure. Rats co-administered amphetamine and MK-801 displayed lower and dose-dependent 50kHz USV emissions, but not lower locomotor activity, during repeated treatment and challenge, and scarce conditioned vocalization compared with amphetamine-treated rats. These effects were associated with lower levels of Zif-268 after amphetamine challenge and spontaneous alternation deficits. CONCLUSIONS: These results indicate that glutamate transmission participates in the acute, long-term, and conditioned effects of amphetamine on 50kHz USVs, possibly by influencing amphetamine-induced long-term neuronal changes and/or amphetamine-associated memories

A versatile facility for the calibration of X-ray polarimeters with polarized and unpolarized controlled beams

We devised and built a versatile facility for the calibration of the next generation X-ray polarimeters with unpolarized and polarized radiation. The former is produced at 5.9 keV by means of a Fe55 radioactive source or by X-ray tubes, while the latter is obtained by Bragg diffraction at nearly 45 degrees. Crystals tuned with the emission lines of X-ray tubes with molybdenum, rhodium, calcium and titanium anodes are employed for the efficient production of highly polarized photons at 2.29, 2.69, 3.69 and 4.51 keV respectively. Moreover the continuum emission is exploited for the production of polarized photons at 1.65 keV and 2.04 keV and at energies corresponding to the higher orders of diffraction. The photons are collimated by means of interchangeable capillary plates and diaphragms, allowing a trade-off between collimation and high fluxes. The direction of the beam is accurately arranged by means of high precision motorized stages, controlled via computer so that long and automatic measurements can be done. Selecting the direction of polarization and the incidence point we can map the response of imaging devices to both polarized and unpolarized radiation. Changing the inclination of the beam we can study the systematic effects due to the focusing of grazing incidence optics and the feasibility of instruments with large field of view.Comment: 12 pages, 11 figure

Lapex: A Phoswich balloon experiment for hard X-ray astronomy

Satellite and balloon observations have shown that several classes of celestial objects are hard ( 15 keV) energy band with a sensitivity of approx 10 mCrab has been performed with the UCSD/MIT instrument (A4) on board the HEAO 1 satellite. About 70 X-ray sources were detected, including galactic and extragalactic objects. Hard X-ray emission has been detected in the Galaxy from X-ray pulsars. Extragalactic sources of hard X-ray emission include clusters of galaxies, QSOs, BL Lac objects, Seyfert galaxies. The essential characteristics of the Large Area Phoswich Experiment (LAPEX) for crowded sky field observations are described. It has: (1) a broad energy band of operation (20-300 keV); (2) a 3 sigma sensitivity of about 1 mCrab in 10,000 s of live observing time; and (3) imaging capabilities with an angular resolution of about 20'

Involvement of the protein ras homolog enriched in the striatum, rhes, in dopaminergic neurons’ degeneration: Link to parkinson’s disease

Rhes is one of the most interesting genes regulated by thyroid hormones that, through the inhibition of the striatal cAMP/PKA pathway, acts as a modulator of dopamine neurotransmission. Rhes mRNA is expressed at high levels in the dorsal striatum, with a medial‐to‐lateral expression gradient reflecting that of both dopamine D2 and adenosine A2A receptors. Rhes transcript is also present in the hippocampus, cerebral cortex, olfactory tubercle and bulb, substantia nigra pars compacta (SNc) and ventral tegmental area of the rodent brain. In line with Rhes‐dependent regulation of dopaminergic transmission, data showed that lack of Rhes enhanced cocaine‐ and am-phetamine‐induced motor stimulation in mice. Previous studies showed that pharmacological de-pletion of dopamine significantly reduces Rhes mRNA levels in rodents, non‐human primates and Parkinson’s disease (PD) patients, suggesting a link between dopaminergic innervation and physiological Rhes mRNA expression. Rhes protein binds to and activates striatal mTORC1, and modulates L‐DOPA‐induced dyskinesia in PD rodent models. Finally, Rhes is involved in the survival of mouse midbrain dopaminergic neurons of SNc, thus pointing towards a Rhes‐dependent modulation of autophagy and mitophagy processes, and encouraging further investigations about mechanisms underlying dysfunctions of the nigrostriatal system

IRQ Coloring and the Subtle Art of Mitigating Interrupt-generated Interference

Integrating workloads with differing criticality levels presents a formidable challenge in achieving the stringent spatial and temporal isolation requirements imposed by safety-critical standards such as ISO26262. The shift towards high-performance multicore platforms has been posing increasing issues to the so-called mixed-criticality systems (MCS) due to the reciprocal interference created by consolidated subsystems vying for access to shared (microarchitectural) resources (e.g., caches, bus interconnect, memory controller). The research community has acknowledged all these challenges. Thus, several techniques, such as cache partitioning and memory throttling, have been proposed to mitigate such interference; however, these techniques have some drawbacks and limitations that impact performance, memory footprint, and availability. In this work, we look from a different perspective. Departing from the observation that safety-critical workloads are typically event- and thus interrupt-driven, we mask "colored" interrupts based on the \ac{QoS} assessment, providing fine-grain control to mitigate interference on critical workloads without entirely suspending non-critical workloads. We propose the so-called IRQ coloring technique. We implement and evaluate the IRQ Coloring on a reference high-performance multicore platform, i.e., Xilinx ZCU102. Results demonstrate negligible performance overhead, i.e., <1% for a 100 microseconds period, and reasonable throughput guarantees for medium-critical workloads. We argue that the IRQ coloring technique presents predictability and intermediate guarantees advantages compared to state-of-art mechanismsComment: 10 pages, 9 figures, 2 table

IRQ Coloring: Mitigating Interrupt-Generated Interference on ARM Multicore Platforms

Mixed-criticality systems, which consolidate workloads with different criticalities, must comply with stringent spatial and temporal isolation requirements imposed by safety-critical standards (e.g., ISO26262). This, per se, has proven to be a challenge with the advent of multicore platforms due to the inner interference created by multiple subsystems while disputing access to shared resources. With this work, we pioneer the concept of Interrupt (IRQ) coloring as a novel mechanism to minimize the interference created by co-existing interrupt-driven workloads. The main idea consists of selectively deactivating specific ("colored") interrupts if the QoS of critical workloads (e.g., Virtual Machines) drops below a well-defined threshold. The IRQ Coloring approach encompasses two artifacts, i.e., the IRQ Coloring Design-Time Tool (IRQ DTT) and the IRQ Coloring Run-Time Mechanism (IRQ RTM). In this paper, we focus on presenting the conceptual IRQ coloring design, describing the first prototype of the IRQ RTM on Bao hypervisor, and providing initial evidence about the effectiveness of the proposed approach on a synthetic use case

A categorification of Morelli's theorem

We prove a theorem relating torus-equivariant coherent sheaves on toric varieties to polyhedrally-constructible sheaves on a vector space. At the level of K-theory, the theorem recovers Morelli's description of the K-theory of a smooth projective toric variety. Specifically, let $X$ be a proper toric variety of dimension $n$ and let M_\bR = \mathrm{Lie}(T_\bR^\vee)\cong \bR^n be the Lie algebra of the compact dual (real) torus T_\bR^\vee\cong U(1)^n. Then there is a corresponding conical Lagrangian \Lambda \subset T^*M_\bR and an equivalence of triangulated dg categories \Perf_T(X) \cong \Sh_{cc}(M_\bR;\Lambda), where \Perf_T(X) is the triangulated dg category of perfect complexes of torus-equivariant coherent sheaves on $X$ and \Sh_{cc}(M_\bR;\Lambda) is the triangulated dg category of complex of sheaves on M_\bR with compactly supported, constructible cohomology whose singular support lies in $\Lambda$. This equivalence is monoidal---it intertwines the tensor product of coherent sheaves on $X$ with the convolution product of constructible sheaves on M_\bR.Comment: 20 pages. This is a strengthened version of the first half of arXiv:0811.1228v3, with new results; the second half becomes arXiv:0811.1228v