Differential Interleukin-2 Transcription Kinetics Render Mouse but Not Human T Cells Vulnerable to Splicing Inhibition Early after Activation

T cells are nodal players in the adaptive immune response against pathogens and malignant cells. Alternative splicing plays a crucial role in T cell activation, which is analyzed mainly at later time points upon stimulation. Here we have discovered a 2-h time window early after stimulation where optimal splicing efficiency or, more generally, gene expression efficiency is crucial for successful T cell activation. Reducing the splicing efficiency at 4 to 6 h poststimulation significantly impaired murine T cell activation, which was dependent on the expression dynamics of the Egr1-Nab2-interleukin-2 (IL-2) pathway. This time window overlaps the time of peak IL-2 de novo transcription, which, we suggest, represents a permissive time window in which decreased splicing (or transcription) efficiency reduces mature IL-2 production, thereby hampering murine T cell activation. Notably, the distinct expression kinetics of the Egr1-Nab2-IL-2 pathway between mouse and human render human T cells refractory to this vulnerability. We propose that the rational temporal modulation of splicing or transcription during peak de novo expression of key effectors can be used to fine-tune stimulation-dependent biological outcomes. Our data also show that critical consideration is required when extrapolating mouse data to the human system in basic and translational research

International Investment Performance: Evidence from Institutional Investors’ Foreign Equity Holdings

This paper analyzes the international equity holdings of a large panel of UK pension funds. We find considerable evidence of market timing activity, as illustrated by the funds’ decision to scale back their investments in the US stock market during the 1990s. To explain this we jointly model time-varying conditional moments and portfolio weight dynamics. Past returns do not adequately explain the funds’ international portfolio flows and only matter for the short run. Instead we find that a substantial part of the evolution in portfolio weights is explained by time-varying conditional expected returns, volatilities and covariances with domestic equity returns. However, once we control for publicly known state variables, there is no evidence of extra-market timing skills and most funds appear to have earned small but negative returns from international market timing

Preserving the measure of compatibility between quantum states

In this paper after defining the abstract concept of compatibility-like functions on quantum states, we prove that every bijective transformation on the set of all states which preserves such a function is implemented by an either unitary or antiunitary operator.Comment: 11 pages, submitted for publicatio

Interferometry of direct photons in Pb+Pb collisions at 158 AGeV

We present final results from the WA98 experiment which provide first measurements of Bose-Einstein correlations of direct photons in ultrarelativistic heavy ion collisions. Invariant interferometric radii were extracted in the range $100<K_T<300$ MeV/c and compared to interferometric radii of charged pions. The yield of direct photons for $100<p_T<300$ MeV/c was extracted from the correlation strength parameter and compared to the yield of direct photons measured in WA98 at higher $p_T$ with the statistical subtraction method, and to predictions of a fireball model.Comment: 4 pages, 3 figures, proceedings for Quark Matter 200

The Ratio of Ortho- to Para-H2 in Photodissociation Regions

We discuss the ratio of ortho- to para-H2 in photodissociation regions (PDRs). We draw attention to an apparent confusion in the literature between the ortho-to-para ratio of molecules in FUV-pumped vibrationally excited states, and the H2 ortho-to-para abundance ratio. These ratios are not the same because the process of FUV-pumping of fluorescent H2 emission in PDRs occurs via optically thick absorption lines. Thus, gas with an equilibrium ratio of ortho- to para-H2 equal to 3 will yield FUV-pumped vibrationally excited ortho-to-para ratios smaller than 3, because the ortho-H2 pumping rates are preferentially reduced by optical depth effects. Indeed, if the ortho and para pumping lines are on the ``square root'' part of the curve-of-growth, then the expected ratio of ortho and para vibrational line strengths is the square root of 3, ~ 1.7, close to the typically observed value. Thus, contrary to what has sometimes been stated in the literature, most previous measurements of the ratio of ortho- to para-H2 in vibrationally excited states are entirely consistent with a total ortho-to-para ratio of 3, the equilibrium value for temperatures greater than 200 K. We present an analysis and several detailed models which illustrate the relationship between the total ratios of ortho- to para-H2 and the vibrationally excited ortho-to-para ratios in PDRs. Recent Infrared Space Observatory (ISO) measurements of pure rotational and vibrational H2 emissions from the PDR in the star-forming region S140 provide strong observational support for our conclusions.Comment: 23 pages (including 5 figures), LaTeX, uses aaspp4.sty, accepted for publication in Ap

(ÿ)-Fern-7-en-3a-ol from Sebastiania brasiliensis

The structure of a fernane isolated from S. brasiliensis was established as fern-7en-3[alpha]-ol, C30H50O. Rings A and D assume a chair conformation, while rings B and C adopt a twist-boat conformation. Rings A/B, C/D, and D/E are trans fused. The relative orientation of the hydroxy group and that of the iso­propyl group is [alpha].This structure was determined in the Molecular Structure Laboratory of the Department of Chemistry, University of Arizona, Tucson, AZ 85721, USA. The SMART1000 diffractometer was gratefully obtained with funds provided by NSF grant CHE9610374. This study was supported by NIH grant 5U01TW00316-10 awarded to BNT. This study was undertaken as part of the required course work for the class CHEM 517 offered by Dr J. H. Enemark at the University of Arizona. The authors thank Liliya Yatsunyk for her help in this study

Correction to: The hidden therapist: evidence for a central role of music in psychedelic therapy.

The article The hidden therapist: evidence for a central role of music in psychedelic therapy, written by Mendel Kaelen, Bruna Giribaldi, Jordan Raine, Lisa Evans, Christopher Timmerman, Natalie Rodriguez, Leor Roseman, Amanda Feilding, David Nutt, Robin Carhart-Harris, was originally published electronically on the publisher's internet portal

Network Centrality and Delegated Investment Performance

We document a positive relation between network centrality and risk-adjusted performance in a delegated investment management setting. More connected managers take more portfolio risk and receive higher investor flows, consistent with these managers improving their ability to exploit investment opportunities through their network connections. Greater network connections are shown to be particularly important in reducing the diseconomies-of-scale for large managers who are well-connected. We also use the exogenous merger of two investment consultants, which creates a sudden change in the network connections of the managers they oversee, to provide evidence that a greater number of connections translates into better portfolio performance

(4R,4aR,6S,7S,7aS)-6-Hydroxy-7-hy- droxymethyl-4-methylperhydrocyclo- penta[c]pyran-1-one chloroform solvate from Valeriana laxiflora

The structure of an iridolactone isolated from Valeriana laxiflora was established as (4R,4aR,6S,7S,7aS)-6-hydroxy-7-hydroxy­methyl-4-methyl­per­hydro­cyclo­penta­[c]­pyran-1-one chloro­form solvate, C10H16O4·CHCl3. The two rings are cis-fused. The [delta]-lactone ring adopts a slightly twisted half-chair conformation with approximate planarity of the lactone group and the cyclo­pentane ring adopts an envelope conformation. The hydroxy group, the hydroxymethyl group and the methyl group all have [beta] orientations. The absolute configuration was determined using anomalous dispersion data enhanced by the adventitious inclusion of a chloro­form solvent mol­ecule. Hydro­gen bonding, crystal packing and ring conformations are discussed in detail.The structure of the title compound was determined in the Molecular Structure Laboratory of the Department of Chemistry, University of Arizona. The diffractometer was obtained with funds provided by the NSF (grant No. CHE9610374). This study was supported by NIH grant No. 5U01TW00316-10 awarded to BNT

Climate of the Past Open Access Using palaeo-climate comparisons to constrain future projections

www.clim-past.net/10/221/2014/ doi:10.5194/cp-10-221-2014 © Author(s) 2014. CC Attribution 3.0 License