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The 18 kDa translocator protein (TSPO) is a highly conserved protein located in the outer mitochondrial membrane. TSPO binding, as measured with positron emission tomography (PET), is considered an in vivo marker of neuroinflammation. Indeed, TSPO expression is altered in neurodegenerative, neuroinflammatory, and neuropsychiatric diseases. In PET studies, the TSPO signal is often viewed as a marker of microglial cell activity. However, there is little evidence in support of a microglia-specific TSPO expression. This review describes the cellular sources and functions of TSPO in animal models of disease and human studies, in health, and in central nervous system diseases. A discussion of methods of analysis and of quantification of TSPO is also presented. Overall, it appears that the alterations of TSPO binding, their cellular underpinnings, and the functional significance of such alterations depend on many factors, notably the pathology or the animal model under study, the disease stage, and the involved brain regions. Thus, further studies are needed to fully determine how changes in TSPO binding occur at the cellular level with the ultimate goal of revealing potential therapeutic pathways. [ABSTRACT FROM AUTHOR]

Background: In hepatobiliary imaging, systems detect the total amount of agents originating from extracellular space, bile canaliculi, and hepatocytes. They add in situ concentration of each compartment corrected by its respective volume ratio to provide liver concentrations. In vivo contribution of each compartment to liver concentration is inaccessible. Our aim was to quantify the compartmental distribution of two hepatobiliary agents in an ex vivo model and determine how their liver extraction ratios and cholestasis (livers lacking canalicular transporters) might modify it. Methods: We perfused labelled gadobenate dimeglumine (Bopta, 200 μM, 7% liver extraction ratio) and mebrofenin (Meb, 64 μM, 94% liver extraction ratio) in normal (n = 18) and cholestatic (n = 6) rat livers. We quantified liver concentrations with a gamma counter placed over livers. Concentrations in hepatocytes and bile canaliculi were calculated. Mann-Whitney and Kruskal-Wallis tests were used. Results: Hepatocyte concentrations were 2,043 ± 333 μM (Meb) versus 360 ± 69 μM (Bopta, p < 0.001). Meb extracellular concentrations did not contribute to liver concentrations (1.3 ± 0.3%). The contribution of Bopta extracellular concentration was 12.4 ± 1.9% (p < 0.001 versus Meb). Contribution of canaliculi was similar for both agents (16%). Cholestatic livers had no Bopta in canaliculi but their hepatocyte concentrations increased in comparison to normal livers. Conclusion: Hepatocyte concentrations are correlated to liver extraction ratios of hepatobiliary agents. When Bopta is not present in canaliculi of cholestatic livers, hepatocyte concentrations increase in comparison to normal livers. This new understanding extends the interpretation of clinical liver images. [ABSTRACT FROM AUTHOR]

Background: [123I]epidepride is a high-affinity radiotracer used in single-photon emission computed tomography (SPECT) imaging of the D2/3 receptors. It binds with high affinity to striatal and extrastriatal receptors. Nevertheless, its slow kinetics in the striatum impedes quantification in this region. Thus, an approach that would allow a simultaneous quantification of both striatal and extrastriatal D2/3 receptors would be of interest for preclinical and clinical SPECT neuroimaging. We describe a partial saturation protocol that allows us to produce an in vivo Scatchard plot and thus estimate Bavail and appKd separately in both striatal and extrastriatal regions, through a single dynamic SPECT session. To validate this approach, a multi-injection protocol is used for the full kinetic modeling of [123I]epidepride using a two-tissue compartment, 5-parameter model (2T-5k). Methods: Eighteen male rats were used. Binding parameters were estimated using the multi-injection protocol. Various simulations were performed to estimate the optimal conditions for the partial saturation protocol, which was applied at the region and voxel level. The results of the partial saturation study were compared to those obtained with the 2T-5k model. To illustrate the interest of the partial saturation approach, we performed a preliminary study of the effect of a chronic, subcutaneous administration of haloperidol (1 mg/kg/day), a D2 receptor antagonist, on the Bavail of [123I]epidepride in the rat striatum. Results: A series of simulations demonstrated that a mass of 3 ug/kg of unlabeled epidepride allows the formation of an in vivo Scatchard plot. The partial saturation study led to robust estimations of Bavail in all brain regions that highly correlated (r = 0.99) with the corresponding values from the multi-injection study. A chronic haloperidol treatment resulted in a 17.9% increase in the Bavail values in the left Caudate Putamen nucleus (CP) (p = 0.07) and a 13.8% increase in the right CP (p = 0.12). Conclusion: A partial saturation method allowed the robust quantification of D2/3 receptors in striatal and extrastriatal D2/3 receptors with a single-scan approach. This approach may be applied in the mapping of the D2/3 receptor in translational biological studies and potentially, in clinical SPECT imaging. [ABSTRACT FROM AUTHOR]

This paper proposes a hardware memory management unit to implement an on-chip message passing protocol for cluster based multi-processors system on chip architectures. Within the architecture each cluster is composed of general purpose processors or digital signal processors, along with a memory. To maintain the coherence of the memory a hardware memory management unit is added in the cluster to increase the performance and support an on-chip message passing communication. The hardware memory management unit has the capacity to allocate, control and limit the access to the memory. In order to show the benefit of our architecture a performance comparison over a classical flat architecture and against a state of the art architecture is driven. The results show an improvement that ranges from 1.2 to 21.77 % over these two architectural models. Finally the hardware cost overhead is studied. [ABSTRACT FROM AUTHOR]

Δ9-Tetrahydrocannabinol (THC), through its action on cannabinoid type-1 receptor (CB1R), is known to activate dopamine (DA) neurotransmission. Functional evidence of a direct antagonistic interaction between CB1R and DA D2-receptors (D2R) suggests that D2R may be an important target for the modulation of DA neurotransmission by THC. The current study evaluated, in rodents, the effects of chronic exposure to THC (1 mg/kg/day; 21 days) on D2R and D3R availabilities using the D2R-prefering antagonist and the D3R-preferring agonist radiotracers [18F]fallypride and [3H]-(+)-PHNO, respectively. At 24 h after the last THC dose, D2R and D3R densities were significantly increased in midbrain. In caudate/putamen (CPu), THC exposure was associated with increased densities of D2R with no change in D2R mRNA expression, whereas in nucleus accumbens (NAcc) both D3R binding and mRNA levels were upregulated. These receptor changes, which were completely reversed in CPu but only partially reversed in NAcc and midbrain at 1 week after THC cessation, correlated with an increased functionality of D2/3R in vivo, based on findings of increased locomotor suppressive effect of a presynaptic dose and enhanced locomotor activation produced by a postsynaptic dose of quinpirole. Concomitantly, the observations of a decreased gene expression of tyrosine hydroxylase in midbrain together with a blunted psychomotor response to amphetamine concurred to indicate a diminished presynaptic DA function following THC. These findings indicate that the early period following THC treatment cessation is associated with altered presynaptic D2/3R controlling DA synthesis and release in midbrain, with the concurrent development of postsynaptic D2/3R supersensitivity in NAcc and CPu. Such D2/3R neuroadaptations may contribute to the reinforcing and habit-forming properties of THC. [ABSTRACT FROM AUTHOR]

Reconfigurable computing offers a wide range of low cost and efficient solutions for embedded systems. The proper choice of the reconfigurable device, the granularity of its processing elements and its memory architecture highly depend on the type of application and their data flow. Existing solutions either offer fine grain FPGAs, which rely on a hardware synthesis flow and offer the maximum degree of flexibility, or coarser grain solutions, which are usually more suitable for a particular type of data flow and applications. In this paper, we present the MORPHEUS architecture, a versatile reconfigurable heterogeneous System-on-Chip targeting streaming applications. The presented architecture exploits different reconfigurable technologies at several computation granularities that efficiently address the different applications needs. In order to efficiently exploit the presented architecture, we implemented a complete software solution to map C applications to the reconfigurable architecture. In this paper, we describe the complete toolset and provide concrete use cases of the architecture. [ABSTRACT FROM AUTHOR]