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We present the first dynamical mass estimates and scaling relations for a sample of Sunyaev-Zel'dovich Effect (SZE) selected galaxy clusters. The sample consists of 16 massive clusters detected with the Atacama Cosmology Telescope (ACT) over a 455 deg 2 area of the southern sky. Deep multi-object spectroscopic observations were taken to secure intermediate-resolution (R ∼ 700-800) spectra and redshifts for ≈ 60 member galaxies on average per cluster. The dynamical masses M 200c of the clusters have been calculated using simulation-based scaling relations between velocity dispersion and mass. The sample has a median redshift z = 0.50 and a median mass M 200c 12 × 10 14 h −1 70 M with a lower limit M 200c 6 × 10 14 h −1 70 M , consistent with the expectations for the ACT southern sky survey. These masses are compared to the ACT SZE properties of the sample, specifically, the match-filtered central SZE amplitude y 0 , the central Compton parameter y 0 , and the integrated Compton signal Y 200c , which we use to derive SZE-mass scaling relations. All SZE estimators correlate with dynamical mass with low intrinsic scatter ( 20%), in agreement with numerical simulations. We explore the effects of various systematic effects on these scaling relations, including the correlation between observables and the influence of dynamically disturbed clusters. Using the three-dimensional information available, we divide the sample into relaxed and disturbed clusters and find that ∼ 50% of the clusters are disturbed. There are hints that disturbed systems might bias the scaling relations but given the current sample sizes these differences are not significant; further studies including more clusters are required to assess the impact of these clusters on the scaling relations. z red / z all J 0 1 0 2 J 0 2 1 5 J 0 2 3 2 J 0 2 3 5 J 0 2 3 7 J 0 3 0 4 J 0 3 3 0 J 0 3 4 6 J 0 4 3 8 J 0 5 0 9 J 0 5 2 1 J 0 5 2 8 J 0 5 4 6 J 0 5 5 9 J 0 6 1 6 J 0 7 0 7

We present optical and X-ray properties for the first confirmed galaxy cluster sample selected by the Sunyaev-Zel'dovich effect (SZE) from 148 GHz maps over 455 deg 2 of sky made with the Atacama Cosmology Telescope (ACT). These maps, coupled with multi-band imaging on 4 m class optical telescopes, have yielded a sample of 23 galaxy clusters with redshifts between 0.118 and 1.066. Of these 23 clusters, 10 are newly discovered. The selection of this sample is approximately mass limited and essentially independent of redshift. We provide optical positions, images, redshifts, and X-ray fluxes and luminosities for the full sample, and X-ray temperatures of an important subset. The mass limit of the full sample is around 8.0×1014 M , with a number distribution that peaks around a redshift of 0.4. For the 10 highest significance SZE-selected cluster candidates, all of which are optically confirmed, the mass threshold is 1 × 10 15 M and the redshift range is 0.167-1.066. Archival observations from Chandra, XMM-Newton, and ROSAT provide X-ray luminosities and temperatures that are broadly consistent with this mass threshold. Our optical follow-up procedure also allowed us to assess the purity of the ACT cluster sample. Eighty (one hundred) percent of the 148 GHz candidates with signal-to-noise ratios greater than 5.1 (5.7) are confirmed as massive clusters. The reported sample represents one of the largest SZE-selected sample of massive clusters over all redshifts within a cosmologically significant survey volume, which will enable cosmological studies as well as future studies on the evolution, morphology, and stellar populations in the most massive clusters in the universe.

To elucidate the role of extracellular histidines in the modulation of the rat P2X 4 receptor by trace metals, we generated single, double, and triple histidine mutants for residues 140, 241, and 286, replacing them with alanines. cDNAs for the wild-type and receptor mutants were expressed in Xenopus laevis oocytes and in human embryonic kidney 293 cells and examined by the two electrode and patch clamp techniques, respectively. Whereas copper inhibited concentration-dependently the ATP-gated currents in the wild-type and in the single or double H241A and H286A receptor mutants, all receptors containing H140A were insensitive to copper in both cell systems. The characteristic bell-shaped concentration-response curve of zinc observed in the wildtype receptor became sigmoid in both oocytes and human embryonic kidney cells expressing the H140A mutant; in these mutants, the zinc potentiation was 2.5-4-fold larger than in the wild-type. Results with the H140T and H140R mutants further support the importance of a histidine residue at this position. We conclude that His-140 is critical for the action of copper, indicating that this histidine residue, but not His-241 or His-286, forms part of the inhibitory allosteric metal-binding site of the P2X 4 receptor, which is distinct from the putative zinc facilitator binding site.The notion that trace metals such as zinc or copper are atypical brain messengers has attracted much attention in view of their emerging role in the modulation of brain excitability (1). The importance of trace metals in synaptic activity is highlighted by the description that both copper and zinc are stored in synaptic vesicles from where they are released by electrical depolarization, reaching a high micromolar concentration at the synaptic cleft (2-4). Trace metals are known to modulate a wide variety of brain ionotropic receptors such as glycine, N-methyl-D-aspartate, ␥-aminobutyric acid, nicotinic, and the novel nucleotide receptors (P2X) family (5-9). The P2X purinoceptors are homomeric or heteromeric membrane channels gated by extracellular ATP and related synthetic nucleotides; North (10) recently reviewed the principles of the molecular physiology of this family of receptors. Within the P2X receptor family, the P2X 4 is the most widely distributed in the central nervous system, including the cerebellum and the CA1 region of the hippocampus, where it has been proposed to play a role in glutamatergic synapses (11).The P2X 4 receptor is an interesting model of an ionic channel differentially modulated by trace metals. Acuñ a-Castillo et al. (12) and Coddou et al. (13) reported that zinc potentiates the ATP-evoked currents whereas copper has an inhibitory effect on the activity of this receptor. Based on these findings, Acuñ aCastillo et al. (12) proposed that trace metals modulate the activity of the P2X 4 receptor via two separate metal-binding sites. One of these sites has a preferential selectivity for copper and is characterized by a non-competitive inhibition of the ATP-gated channel acti...

To further analyze the action of copper on brain synaptic mechanisms, the brain dipeptide carnosine (b-alanyl-L-histidine) was tested in Xenopus laevis oocytes expressing the rat P2X 4 or P2X 7 receptors. Ten micromolar copper halved the currents evoked by ATP in both receptors; co-application of carnosine plus copper prevented the metal induced-inhibition with a median effective concentration of 12.1 3.9 and 12.0 5.5 lM for P2X 4 and P2X 7 , respectively. Zinc potentiated only the P2X 4 ATP-evoked currents; carnosine had no effect over this metal. The relative potency and selectivity of classical metal chelators to prevent the copper inhibition was compared between carnosine and penicillamine (PA), bathophenanthroline (BPh) or L-histidine (His). Their rank order of potency in P2X 4 and P2X 7 receptors was carnosine PA His > BPh > Glycine (Gly) and carnosine BPh His > PA > Gly, respectively. The potency to prevent the zinc-induced potentiation in the P2X 4 receptor was BPh > PA > His; carnosine, Gly and b-alanine were inactive. Whereas 1±100 lM carnosine or His alone did not modify the ATP-evoked currents, 10±100 lM PA augmented and 100 lM BPh decreased the ATP-evoked currents. Carnosine was able to revert the copper-induced inhibition restoring the maximal ATP gated current in a concentration-dependent manner. Electronic spectroscopy con®rm the formation of carnosine-Cu(II) complexes, mechanism that can account for the prevention and reversal of the copper inhibition, revealing its potential in copper intoxication treatment.

The heme oxygenase (HO) system involves three isoforms of this enzyme, HO-1, HO-2, and HO-3. The three of them display the same catalytic activity, oxidating the heme group to produce biliverdin, ferrous iron, and carbon monoxide (CO). HO-1 is the isoform most widely studied in proinflammatory diseases because treatments that overexpress this enzyme promote the generation of anti-inflammatory products. However, neonatal jaundice (hyperbilirubinemia) derived from HO overexpression led to the development of inhibitors, such as those based on metaloproto- and meso-porphyrins inhibitors with competitive activity. Further, non-competitive inhibitors have also been identified, such as synthetic and natural imidazole-dioxolane-based, small synthetic molecules, inhibitors of the enzyme regulation pathway, and genetic engineering using iRNA or CRISPR cas9. Despite most of the applications of the HO inhibitors being related to metabolic diseases, the beneficial effects of these molecules in immune-mediated diseases have also emerged. Different medical implications, including cancer, Alzheimer´s disease, and infections, are discussed in this article and as to how the selective inhibition of HO isoforms may contribute to the treatment of these ailments.

Equating methods make use of an appropriate transformation function to map the scores of one test form into the scale of another so that scores are comparable and can be used interchangeably. The equating literature shows that the ways of judging the success of an equating (i.e., the score transformation) might differ depending on the adopted framework. Rather than targeting different parts of the equating process and aiming to evaluate the process from different aspects, this article views the equating transformation as a standard statistical estimator and discusses how this estimator should be assessed in an equating framework. For the kernel equating framework, a numerical illustration shows the potentials of viewing the equating transformation as a statistical estimator as opposed to assessing it using equatingspecific criteria. A discussion on how this approach can be used to compare other equating estimators from different frameworks is also included. 106

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