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

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

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

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

A propensity criterion for networking in an array of coupled chaotic systems

We examine the mutual synchronization of a one dimensional chain of chaotic identical objects in the presence of a stimulus applied to the first site. We first describe the characteristics of the local elements, and then the process whereby a global nontrivial behaviour emerges. A propensity criterion for networking is introduced, consisting in the coexistence within the attractor of a localized chaotic region, which displays high sensitivity to external stimuli,and an island of stability, which provides a reliable coupling signal to the neighbors in the chain. Based on this criterion we compare homoclinic chaos, recently explored in lasers and conjectured to be typical of a single neuron, with Lorenz chaos.Comment: 4 pages, 3 figure

ISO observations toward the reflection nebula NGC 7023: A nonequilibrium ortho- to para-H2 ratio

We have observed the S(0), S(1), S(2), S(3), S(4) and S(5) rotational lines of molecular hydrogen (H2) towards the peak of the photodissociation region (PDR) associated with the reflection nebula NGC 7023. The observed H2 line ratios show that they arise in warm gas with kinetic temperatures ~300 - 700 K. However, the data cannot be fitted by an ortho- to para- (OTP) ratio of 3. An OTP ratio in the range ~1.5 - 2 is necessary to explain our observations. This is the first detection of a non-equilibrium OTP ratio measured from the H2 pure-rotational lines in a PDR. The existence of a dynamical PDR is discussed as the most likely explanation for this low OTP ratio.Comment: 4 pages, 3 figure

The Finite Element Sea Ice-Ocean Model (FESOM) v.1.4: formulation of an ocean general circulation model

The Finite Element Sea Ice-Ocean Model (FESOM) is the first global ocean general circulation model based on unstructured-mesh methods that has been developed for the purpose of climate research. The advantage of unstructured-mesh models is their flexible multi-resolution modelling functionality. In this study, an overview of the main features of FESOM will be given; based on sensitivity experiments a number of specific parameter choices will be explained; and directions of future developments will be outlined. It is argued that FESOM is sufficiently mature to explore the benefits of multi-resolution climate modelling and that its applications will provide information useful for the advancement of climate modelling on unstructured meshes

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