Private Accountability and the Fourteenth Amendment; State Action, Federalism and Congress

In this essay, I hope to expand the foundation of that conclusion and further explore its implications for private accountability and the duties of the Court, Congress and state lawmakers. Part I extends the discussion from state responsibility to private accountability. It first examines the paradoxes implicit in the Courts doctrine of private accountability. Among the forces that have shaped the present doctrine of private accountability, and motivated the scholarly debate, is the palpable need to protect the fundamental interests of people against invasion by powerful private initiatives

k-server via multiscale entropic regularization

We present an $O((\log k)^2)$-competitive randomized algorithm for the $k$-server problem on hierarchically separated trees (HSTs). This is the first $o(k)$-competitive randomized algorithm for which the competitive ratio is independent of the size of the underlying HST. Our algorithm is designed in the framework of online mirror descent where the mirror map is a multiscale entropy. When combined with Bartal's static HST embedding reduction, this leads to an $O((\log k)^2 \log n)$-competitive algorithm on any $n$-point metric space. We give a new dynamic HST embedding that yields an $O((\log k)^3 \log \Delta)$-competitive algorithm on any metric space where the ratio of the largest to smallest non-zero distance is at most $\Delta$

Socio-economic status over the life-course and depressive symptoms in men and women in Eastern Europe

Objective: Research into social inequalities in depression has studied western populations but data from non-western countries are sparse. In this paper, we investigate the extent of social inequalities in depression in Eastern Europe, the relative importance of social position at different points of the life-course, and whether social patterning of depression differs between men and women.Method: A cross-sectional study examined 12,053 men and 13,582 women in Russia, Poland and the Czech Republic. Depressive symptoms (16 or above on the CESD-20) were examined in relation to socio-economic circumstances at three phases of the life-course: childhood (household amenities and father's education); own education; current circumstances (financial difficulties and possession of household items).Results: Pronounced social differences in depression exist in men and women throughout Eastern Europe. Depression was largely influenced by current circumstances rather than by early life or education, with effects stronger in Poland and Russia. Odds ratios in men for current disadvantage were 3.16 [95% CI: 2.57-3.89], 3.16 [2.74-3.64] and 2.17 [1.80-2.63] in Russia, Poland and the Czech Republic respectively. Social variables did not explain the female excess in depression, which varied from 2.91 [2.58-3.27] in Russia to 1.90 [1.74-2.08] in Poland. Men were more affected by adult disadvantage than women, leading to narrower sex differentials in the presence of disadvantage.Limitations: Cross-sectional data with recall of childhood conditions were used.Conclusion: Current social circumstances are the strongest influence on increased depressive symptoms in countries which have recently experienced social changes. (C) 2007 Elsevier B.V. All rights reserved

LC-MS/MS analysis of Δ9-THC, CBN and CBD in hair: investigation of artefacts

In forensic toxicology, high-performance liquid chromatography tandem mass spectrometry (LC-MS/MS) is increasingly used for the fast and sensitive measurement of a wide range of drugs. For our routine casework, a liquid chromatography atmospheric pressure chemical ionization-tandem mass spectrometry (LC-APCI-MS/MS) method for the quantification of Δ9-tetrahydrocannabinol (Δ9-THC), cannabinol (CBN) and cannabidiol (CBD) in hair was established and fully validated. Separation was achieved using a Kinetex® C18 column (100 mm × 2.1 mm, 100 Å, 1.7 μm, Phenomenex) at a flow rate of 0.5 mL/min. Measurements were performed on a QTrap 5,500 mass spectrometer (Sciex, Darmstadt, Germany). Unexpected signals were observed in authentic THC-positive hair samples. First, a signal with a slightly shifted retention time of THC whose origin could be assigned to the isomer Δ8-THC. Second, additional peaks exhibiting the same fragments as CBN and Δ9-THC but eluting at different retention times were detected. Spiking experiments and enhanced product ion scans (EPI) pointed to the origin of these additional signals as result of in-source decarboxylation of Δ9-tetrahydrocannabinolic acid A (Δ9-THCA-A) into Δ9-THC and further partial oxidation of Δ9-THC into CBN, respectively. Positive findings of Δ9-THCA-A in hair have been shown to derive from external contamination, therefore, the herein described artefacts may be used as indirect markers for external contamination

Potentiation of Glycine-Gated NR1/NR3A NMDA Receptors Relieves Ca2+-Dependent Outward Rectification

Glycine has diverse functions within the mammalian central nervous system. It inhibits postsynaptic neurons via strychnine-sensitive glycine receptors (GlyRs) and enhances neuronal excitation through co-activation of N-methyl-D-aspartate (NMDA) receptors. Classical Ca2+-permeable NMDA receptors are composed of glycine-binding NR1 and glutamate-binding NR2 subunits, and hence require both glutamate and glycine for efficient activation. In contrast, recombinant receptors composed of NR1 and the glycine binding NR3A and/or NR3B subunits lack glutamate binding sites and can be activated by glycine alone. Therefore these receptors are also named “excitatory glycine receptors”. Co-application of antagonists of the NR1 glycine-binding site or of the divalent cation Zn2+ markedly enhances the glycine responses of these receptors. To gain further insight into the properties of these glycine-gated NMDA receptors, we investigated their current-voltage (I–V) dependence. Whole-cell current-voltage relations of glycine currents recorded from NR1/NR3B and NR1/NR3A/NR3B expressing oocytes were found to be linear under our recording conditions. In contrast, NR1/NR3A receptors displayed a strong outwardly rectifying I–V relation. Interestingly, the voltage-dependent inward current block was abolished in the presence of NR1 antagonists, Zn2+ or a combination of both. Further analysis revealed that Ca2+ (1.8 mM) present in our recording solutions was responsible for the voltage-dependent inhibition of ion flux through NR1/NR3A receptors. Since physiological concentrations of the divalent cation Mg2+ did not affect the I–V dependence, our data suggest that relief of the voltage-dependent Ca2+ block of NR1/NR3A receptors by Zn2+ may be important for the regulation of excitatory glycinergic transmission, according to the Mg2+-block of conventional NR1/NR2 NMDA receptors

Microglial ramification, surveillance and interleukin-1beta release are regulated by the two-pore domain K+ channel THIK-1

Microglia exhibit two modes of motility: they constantly extend and retract their processes to survey the brain, but they also send out targeted processes to envelop sites of tissue damage. We now show that these motility modes differ mechanistically. We identify the two-pore domain channel THIK-1 as the main K+ channel expressed in microglia in situ. THIK-1 is tonically active, and its activity is potentiated by P2Y12 receptors. Inhibiting THIK-1 function pharmacologically or by gene knockout depolarizes microglia, which decreases microglial ramification and thus reduces surveillance, whereas blocking P2Y12 receptors does not affect membrane potential, ramification, or surveillance. In contrast, process outgrowth to damaged tissue requires P2Y12 receptor activation but is unaffected by blocking THIK-1. Block of THIK-1 function also inhibits release of the pro-inflammatory cytokine interleukin-1β from activated microglia, consistent with K+ loss being needed for inflammasome assembly. Thus, microglial immune surveillance and cytokine release require THIK-1 channel activity