High-redshift star formation rate up to z~8.3 derived from gamma-ray bursts and influence of background cosmology

The high-redshift star formation rate (SFR) is difficult to measure directly even by modern approaches. Long-duration gamma-ray bursts (GRBs) can be detected to the edge of the visible universe because of their high luminorsities. The collapsar model of long gamma-ray bursts indicates that they may trace the star formation history. So long gamma-ray bursts may be a useful tool of measuring the high-redshift SFR. Observations show that long gamma-ray bursts prefer to form in a low-metallicity environment. We study the high-redshift SFR up to z~8.3 considering the Swift GRBs tracing the star formation history and the cosmic metallicity evolution in different background cosmological models including $\Lambda$CDM, quintessence, quintessence with a time-varying equation of state, and brane-world model. We use latest Swift GRBs including two highest-$z$ GRBs, GRB 080913 at $z=6.7$ and GRB 090423 at $z=8.3$. We find that the SFR at $z>4$ shows a steep decay with a slope of $\sim -5.0$ in $\Lambda$CDM. In the other three models, the high-redshift SFR is slightly different from $\Lambda$CDM model, and also shows a steep decay.Comment: 5 pages, 5 figures, 2 tables, two references adde

Time evolution in linear response: Boltzmann equations and beyond

In this work a perturbative linear response analysis is performed for the time evolution of the quasi-conserved charge of a scalar field. One can find two regimes, one follows exponential damping, where the damping rate is shown to come from quantum Boltzmann equations. The other regime (coming from multiparticle cuts and products of them) decays as power law. The most important, non-oscillating contribution in our model comes from a 4-particle intermediate state and decays as 1/t^3. These results may have relevance for instance in the context of lepton number violation in the Early Universe.Comment: 19 page

Corticosterone Potentiation of Cocaine-Induced Reinstatement of Conditioned Place Preference in Mice is Mediated by Blockade of the Organic Cation Transporter 3

The mechanisms by which stressful life events increase the risk of relapse in recovering cocaine addicts are not well understood. We previously reported that stress, via elevated corticosterone, potentiates cocaine-primed reinstatement of cocaine seeking following self-administration in rats and that this potentiation appears to involve corticosterone-induced blockade of dopamine clearance via the organic cation transporter 3 (OCT3). In the present study, we use a conditioned place preference/reinstatement paradigm in mice to directly test the hypothesis that corticosterone potentiates cocaine-primed reinstatement by blockade of OCT3. Consistent with our findings following self-administration in rats, pretreatment of male C57/BL6 mice with corticosterone (using a dose that reproduced stress-level plasma concentrations) potentiated cocaine-primed reinstatement of extinguished cocaine-induced conditioned place preference. Corticosterone failed to re-establish extinguished preference alone but produced a leftward shift in the dose–response curve for cocaine-primed reinstatement. A similar potentiating effect was observed upon pretreatment of mice with the non-glucocorticoid OCT3 blocker, normetanephrine. To determine the role of OCT3 blockade in these effects, we examined the abilities of corticosterone and normetanephrine to potentiate cocaine-primed reinstatement in OCT3-deficient and wild-type mice. Conditioned place preference, extinction and reinstatement of extinguished preference in response to low-dose cocaine administration did not differ between genotypes. However, corticosterone and normetanephrine failed to potentiate cocaine-primed reinstatement in OCT3-deficient mice. Together, these data provide the first direct evidence that the interaction of corticosterone with OCT3 mediates corticosterone effects on drug-seeking behavior and establish OCT3 function as an important determinant of susceptibility to cocaine use

Drug delivery across length scales

Over the last century, there has been a dramatic change in the nature of therapeutic, biologically active molecules available to treat disease. Therapies have evolved from extracted natural products towards rationally designed biomolecules, including small molecules, engineered proteins and nucleic acids. The use of potent drugs which target specific organs, cells or biochemical pathways, necessitates new tools which can enable controlled delivery and dosing of these therapeutics to their biological targets. Here, we review the miniaturisation of drug delivery systems from the macro to nano-scale, focussing on controlled dosing and controlled targeting as two key parameters in drug delivery device design. We describe how the miniaturisation of these devices enables the move from repeated, systemic dosing, to on-demand, targeted delivery of therapeutic drugs and highlight areas of focus for the future

Role of Kv1 Potassium Channels in Regulating Dopamine Release and Presynaptic D2 Receptor Function

Dopamine (DA) release in the CNS is critical for motor control and motivated behaviors. Dysfunction of its regulation is thought to be implicated in drug abuse and in diseases such as schizophrenia and Parkinson's. Although various potassium channels located in the somatodendritic compartment of DA neurons such as G-protein-gated inward rectifying potassium channels (GIRK) have been shown to regulate cell firing and DA release, little is presently known about the role of potassium channels localized in the axon terminals of these neurons. Here we used fast-scan cyclic voltammetry to study electrically-evoked DA release in rat dorsal striatal brain slices. We find that although G-protein-gated inward rectifying (GIRK) and ATP-gated (KATP) potassium channels play only a minor role, voltage-gated potassium channels of the Kv1 family play a major role in regulating DA release. The use of Kv subtype-selective blockers confirmed a role for Kv1.2, 1.3 and 1.6, but not Kv1.1, 3.1, 3.2, 3.4 and 4.2. Interestingly, Kv1 blockers also reduced the ability of quinpirole, a D2 receptor agonist, to inhibit evoked DA overflow, thus suggesting that Kv1 channels also regulate presynaptic D2 receptor function. Our work identifies Kv1 potassium channels as key regulators of DA release in the striatum