Early Observations And Analysis Of The Type Ia SN 2014J In M82

We present optical and near infrared (NIR) observations of the nearby Type Ia SN 2014J. Seventeen optical and 23 NIR spectra were obtained from 10 days before (-10d) to 10 days after (+10d) the time of maximum B-band brightness. The relative strengths of absorption features and their patterns of development can be compared at one day intervals throughout most of this period. Carbon is not detected in the optical spectra, but we identify C I lambda 1.0693 in the NIR spectra. Mg II lines with high oscillator strengths have higher initial velocities than other Mg II lines. We show that the velocity differences can be explained by differences in optical depths due to oscillator strengths. The spectra of SN 2014J show that it is a normal SN Ia, but many parameters are near the boundaries between normal and high-velocity subclasses. The velocities for OI, Mg II, Si II, S Ca a, and Fell suggest that SN 2014J has a layered structure with little or no mixing. That result is consistent with the delayed detonation explosion models. We also report photometric observations, obtained from -10d to +29d, in the UBVRIJH and K-s bands. The template fitting package SNooPy is used to interpret the light curves and to derive photometric parameters. Using R-v = 1.46, which is consistent with previous studies, SNooPy finds that A(v) = 1.80 for E(B - V)(host) = 1.23 +/- 0.06 mag. The maximum B-band brightness of -19.19 +/- 0.10 mag was reached on February 1.74 UT +/- 0.13 days and the supernova has a decline parameter, Delta m(15), of 1.12 +/- 0.02 mag.Department of Space, Government of IndiaHungarian OTKA NN-107637NSF AST-1109801, AST-1151462, AST-1211196NSF Astronomy and Astrophysics Postdoctoral Fellowship AST-1302771NASA through a grant from the Space Telescope Science Institute GO-12540NASA NAS5-26555Swedish Research CouncilSwedish National Space BoardDanish Agency for Science and Technology and Innovation realized through a Sapere Aude Level 2 grantAstronom

Early Observations and Analysis of the Type Ia SN 2014J in M82

We present optical and near infrared (NIR) observations of the nearby Type Ia SN 2014J. Seventeen optical and twenty-three NIR spectra were obtained from 10 days before ($-$10d) to 10 days after (+10d) the time of maximum $B$-band brightness. The relative strengths of absorption features and their patterns of development can be compared at one day intervals throughout most of this period. Carbon is not detected in the optical spectra, but we identify CI $\lambda$ 1.0693 in the NIR spectra. We find that MgII lines with high oscillator strengths have higher initial velocities than other MgII lines. We show that the velocity differences can be explained by differences in optical depths due to oscillator strengths. The spectra of SN 2014J show it is a normal SN Ia, but many parameters are near the boundaries between normal and high-velocity subclasses. The velocities for OI, MgII, SiII, SII, CaII and FeII suggest that SN 2014J has a layered structure with little or no mixing. That result is consistent with the delayed detonation explosion models. We also report photometric observations, obtained from $-$10d to +29d, in the $UBVRIJH$ and $K_s$ bands. SN 2014J is about 3 magnitudes fainter than a normal SN Ia at the distance of M82, which we attribute to extinction in the host. The template fitting package SNooPy is used to interpret the light curves and to derive photometric parameters. Using $R_V$ = 1.46, which is consistent with previous studies, SNooPy finds that $A_V = 1.80$ for $E(B-V)_{host}=1.23 \pm 0.01$ mag. The maximum $B$-band brightness of $-19.19 \pm 0.10$ mag was reached on February 1.74 UT $\pm 0.13$ days and the supernova had a decline parameter of $\Delta m_{15}=1.11 \pm 0.02$ mag.Comment: 6 figures, 6 tables, submitted to the Ap

4D Reconstruction and Visualization of Cultural Heritage: Analysing our Legacy Through Time

Temporal analyses and multi-temporal 3D reconstruction are fundamental for the preservation and maintenance of all forms of Cultural Heritage (CH) and are the basis for decisions related to interventions and promotion. Introducing the fourth dimension of time into three-dimensional geometric modelling of real data allows the creation of a multi-temporal representation of a site. In this way, scholars from various disciplines (surveyors, geologists, archaeologists, architects, philologists, etc.) are provided with a new set of tools and working methods to support the study of the evolution of heritage sites, both to develop hypotheses about the past and to model likely future developments. The capacity to “see” the dynamic evolution of CH assets across different spatial scales (e.g. building, site, city or territory) compressed in diachronic model, affords the possibility to better understand the present status of CH according to its history. However, there are numerous challenges in order to carry out 4D modelling and the requisite multi-data source integration. It is necessary to identify the specifications, needs and requirements of the CH community to understand the required levels of 4D model information. In this way, it is possible to determine the optimum material and technologies to be utilised at different CH scales, as well as the data management and visualization requirements. This manuscript aims to provide a comprehensive approach for CH time-varying representations, analysis and visualization across different working scales and environments: rural landscape, urban landscape and architectural scales. Within this aim, the different available metric data sources are systemized and evaluated in terms of their suitability

The Cobalamin-Binding Protein in Zebrafish Is an Intermediate between the Three Cobalamin-Binding Proteins in Human

In humans, three soluble extracellular cobalamin-binding proteins; transcobalamin (TC), intrinsic factor (IF), and haptocorrin (HC), are involved in the uptake and transport of cobalamin. In this study, we investigate a cobalamin-binding protein from zebrafish (Danio rerio) and summarize current knowledge concerning the phylogenetic evolution of kindred proteins. We identified a cobalamin binding capacity in zebrafish protein extracts (8.2 pmol/fish) and ambient water (13.5 pmol/fish) associated with a single protein. The protein showed resistance toward degradation by trypsin and chymotrypsin (like human IF, but unlike human HC and TC). The cobalamin analogue, cobinamide, bound weaker to the zebrafish cobalamin binder than to human HC, but stronger than to human TC and IF. Affinity for another analogue, adenosyl-pseudo-cobalamin was low compared with human HC and TC, but high compared with human IF. The absorbance spectrum of the purified protein in complex with hydroxo-cobalamin resembled those of human HC and IF, but not TC. We searched available databases to further explore the phylogenies of the three cobalamin-binding proteins in higher vertebrates. Apparently, TC-like proteins are the oldest evolutionary derivatives followed by IF and HC (the latter being present only in reptiles and most but not all mammals). Our findings suggest that the only cobalamin-binding protein in zebrafish is an intermediate between the three human cobalamin binders. These findings support the hypothesis about a common ancestral gene for all cobalamin-binding proteins in higher vertebrates

Excitatory effect of ATP on rat area postrema neurons

ATP-induced inward currents and increases in the cytosolic Ca2+ concentration ([Ca]in) were investigated in neurons acutely dissociated from rat area postrema using whole-cell patch-clamp recordings and fura-2 microfluorometry, respectively. The ATP-induced current (IATP) and [Ca]in increases were mimicked by 2-methylthio-ATP and ATP-γS, and were inhibited by P2X receptor (P2XR) antagonists. The current–voltage relationship of the IATP exhibited a strong inward rectification, and the amplitude of the IATP was concentration-dependent. The IATP was markedly reduced in the absence of external Na+, and the addition of Ca2+ to Na+-free saline increased the IATP. ATP did not increase [Ca]in in the absence of external Ca2+, and Ca2+ channel antagonists partially inhibited the ATP-induced [Ca]in increase, indicating that ATP increases [Ca]in by Ca2+ influx through both P2XR channels and voltage-dependent Ca2+ channels. There was a negative interaction between P2XR- and nicotinic ACh receptor (nAChR)-channels, which depended on the amplitude and direction of current flow through either channel. Current occlusion was observed at Vhs between −70 and −10 mV when the IATP and ACh-induced current (IACh) were inward, but no occlusion was observed when these currents were outward at a Vh of +40 mV. The IATP was not inhibited by co-application of ACh when the IACh was markedly decreased either by removal of permeant cations, by setting Vh close to the equilibrium potential of IACh, or by the addition of d-tubocurarine or serotonin. These results suggest that the inhibitory interaction is attributable to inward current flow of cations through the activated P2XR- and nAChR-channels

In Vitro and In Vivo Antagonism of a G Protein-Coupled Receptor (S1P3) with a Novel Blocking Monoclonal Antibody

Background: S1P 3 is a lipid-activated G protein-couple receptor (GPCR) that has been implicated in the pathological processes of a number of diseases, including sepsis and cancer. Currently, there are no available high-affinity, subtypeselective drug compounds that can block activation of S1P3. We have developed a monoclonal antibody (7H9) that specifically recognizes S1P3 and acts as a functional antagonist. Methodology/Principal Findings: Specific binding of 7H9 was demonstrated by immunocytochemistry using cells that over-express individual members of the S1P receptor family. We show, in vitro, that 7H9 can inhibit the activation of S1P3mediated cellular processes, including arrestin translocation, receptor internalization, adenylate cyclase inhibiton, and calcium mobilization. We also demonstrate that 7H9 blocks activation of S1P3 in vivo, 1) by preventing lethality due to systemic inflammation, and 2) by altering the progression of breast tumor xenografts. Conclusions/Significance: We have developed the first-reported monoclonal antibody that selectively recognizes a lipidactivated GPCR and blocks functional activity. In addition to serving as a lead drug compound for the treatment of sepsi

The Effect of a ΔK280 Mutation on the Unfolded State of a Microtubule-Binding Repeat in Tau

Tau is a natively unfolded protein that forms intracellular aggregates in the brains of patients with Alzheimer's disease. To decipher the mechanism underlying the formation of tau aggregates, we developed a novel approach for constructing models of natively unfolded proteins. The method, energy-minima mapping and weighting (EMW), samples local energy minima of subsequences within a natively unfolded protein and then constructs ensembles from these energetically favorable conformations that are consistent with a given set of experimental data. A unique feature of the method is that it does not strive to generate a single ensemble that represents the unfolded state. Instead we construct a number of candidate ensembles, each of which agrees with a given set of experimental constraints, and focus our analysis on local structural features that are present in all of the independently generated ensembles. Using EMW we generated ensembles that are consistent with chemical shift measurements obtained on tau constructs. Thirty models were constructed for the second microtubule binding repeat (MTBR2) in wild-type (WT) tau and a ΔK280 mutant, which is found in some forms of frontotemporal dementia. By focusing on structural features that are preserved across all ensembles, we find that the aggregation-initiating sequence, PHF6*, prefers an extended conformation in both the WT and ΔK280 sequences. In addition, we find that residue K280 can adopt a loop/turn conformation in WT MTBR2 and that deletion of this residue, which can adopt nonextended states, leads to an increase in locally extended conformations near the C-terminus of PHF6*. As an increased preference for extended states near the C-terminus of PHF6* may facilitate the propagation of β-structure downstream from PHF6*, these results explain how a deletion at position 280 can promote the formation of tau aggregates

Probing the urea dependence of residual structure in denatured human α-lactalbumin

Backbone 15N relaxation parameters and 15N–1HN residual dipolar couplings (RDCs) have been measured for a variant of human α-lactalbumin (α-LA) in 4, 6, 8 and 10 M urea. In the α-LA variant, the eight cysteine residues in the protein have been replaced by alanines (all-Ala α-LA). This protein is a partially folded molten globule at pH 2 and has been shown previously to unfold in a stepwise non-cooperative manner on the addition of urea. 15N R2 values in some regions of all-Ala α-LA show significant exchange broadening which is reduced as the urea concentration is increased. Experimental RDC data are compared with RDCs predicted from a statistical coil model and with bulkiness, average area buried upon folding and hydrophobicity profiles in order to identify regions of non-random structure. Residues in the regions corresponding to the B, D and C-terminal 310 helices in native α-LA show R2 values and RDC data consistent with some non-random structural propensities even at high urea concentrations. Indeed, for residues 101–106 the residual structure persists in 10 M urea and the RDC data suggest that this might include the formation of a turn-like structure. The data presented here allow a detailed characterization of the non-cooperative unfolding of all-Ala α-LA at higher concentrations of denaturant and complement previous studies which focused on structural features of the molten globule which is populated at lower concentrations of denaturant