The differential regulation of Lck kinase phosphorylation sites by CD45 is critical for T cell receptor signaling responses

SummaryThe molecular mechanisms whereby the CD45 tyrosine phosphatase (PTPase) regulates T cell receptor (TCR) signaling responses remain to be elucidated. To investigate this question, we have reconstituted CD45 (encoded by Ptprc)-deficient mice, which display severe defects in thymic development, with five different expression levels of transgenic CD45RO, or with mutant PTPase null or PTPase-low CD45R0. Whereas CD45 PTPase activity was absolutely required for the reconstitution of thymic development, only 3% of wild-type CD45 activity restored T cell numbers and normal cytotoxic T cell responses. Lowering the CD45 expression increased CD4 lineage commitment. Peripheral T cells with very low activity of CD45 phosphatase displayed reduced TCR signaling, whereas intermediate activity caused hyperactivation of CD4+ and CD8+ T cells. These results are explained by a rheostat mechanism whereby CD45 differentially regulates the negatively acting pTyr-505 and positively acting pTyr-394 p56lck tyrosine kinase phosphorylation sites. We propose that high wild-type CD45 expression is necessary to dephosphorylate p56lck pTyr-394, suppressing CD4 T+ cell lineage commitment and hyperactivity

Towards a state-space geometry of neural responses to natural scenes: A steady-state approach

Our understanding of information processing by the mammalian visual system has come through a variety of techniques ranging from psychophysics and fMRI to single unit recording and EEG. Each technique provides unique insights into the processing framework of the early visual system. Here, we focus on the nature of the information that is carried by steady state visual evoked potentials (SSVEPs). To study the information provided by SSVEPs, we presented human participants with a population of natural scenes and measured the relative SSVEP response. Rather than focus on particular features of this signal, we focused on the full state-space of possible responses and investigated how the evoked responses are mapped onto this space. Our results show that it is possible to map the relatively high-dimensional signal carried by SSVEPs onto a 2-dimensional space with little loss. We also show that a simple biologically plausible model can account for a high proportion of the explainable variance (~73%) in that space. Finally, we describe a technique for measuring the mutual information that is available about images from SSVEPs. The techniques introduced here represent a new approach to understanding the nature of the information carried by SSVEPs. Crucially, this approach is general and can provide a means of comparing results across different neural recording methods. Altogether, our study sheds light on the encoding principles of early vision and provides a much needed reference point for understanding subsequent transformations of the early visual response space to deeper knowledge structures that link different visual environments

Pulsed Plasma Thruster Technology for Small Satellite Missions

Pulsed plasma thrusters (PPT's) offer the combined benefits of extremely low average electric power requirements (1 to 150 W), high specific impulse (approximately 1000 s), and system simplicity derived from the use of an inert solid propellant. Potential applications range from orbit insertion and maintenance of small satellites to attitude control for large geostationary communications satellites. While PPT's have been used operationally on several spacecraft, there has been no new PPT technology development since the early 1970's. As result of the rapid growth in the small satellite community and the broad range of PPT applications, NASA has initiated a development program with the objective of dramatically reducing the PPT dry mass, increasing PPT performance, and demonstrating a flight ready system by October 1997. This paper presents the results of a series of near-Earth mission studies including both primary and auxiliary propulsion and attitude control functions and reviews the status of NASA's on-going development program

Sites of Biosynthesis of Outer and Inner Membrane Proteins of Neurospora crassa Mitochondria

Outer and inner membranes of Neurospora crassa mitochondria were separated by the combined swelling, shrinking, sonication procedure. Membranes were characterized by electron microscopy and by marker enzyme activities. A red carotenoid pigment was found to be concentrated in the outer membrane. The inner mitochondrial membrane was resolved into about 20 protein bands on polyacrylamide gel electrophoresis, whereas the outer membrane shows essentially one single protein band. Only negligible incorporation of radioactive amino acids occurs into outer membrane when isolated mitochondria are synthesizing polypeptide chains. In agreement with this observation labeling of outer membrane protein is almost entirely blocked, when whole Neurospora cells are incubated with radioactive amino acids in the presence of cycloheximide, an inhibitor of cytoplasmic protein synthesis. Finally, the essential electrophoretic protein band from outer membrane does not become labeled when mitochondria are incubated with radioactive amino acids either in vitro or in vivo in the presence of cycloheximide. It is concluded that the vast majority, if not all, of the outer membrane protein is synthesized by the cytoplasmic system and that polypeptide chains formed by the mitochondrial ribosomes are integrated into the inner mitochondrial membrane

Mathematical literacy in Plant Physiology undergraduates: results of interventions aimed at improving students' performance

The importance of mathematical literacy in any scientific career is widely recognized. However, various studies report lack of numeracy and mathematical literacy in students from various countries. In the present work we present a detailed study of the mathematical literacy of Spanish undergraduate students of Biology enrolled in a Plant Physiology course. We have performed individual analyses of results obtained during the period 2000-2011, for questions in the examinations requiring and not requiring mathematical skills. Additionally, we present the outcome of two interventions introduced with the aim of helping students improve their prospects for success in the course. Our results confirm previous research showing students' deficiencies in mathematical skills. However, the scores obtained for mathematical questions in the examinations are good predictors of the final grades attained in Plant Physiology, as there are strong correlations at the individual level between results for questions requiring and not requiring mathematical skills. The introduction of a laboratory session devoted to strengthening the application of students' previously acquired mathematical knowledge did not change significantly the results obtained for mathematical questions. Since mathematical abilities of students entering university have declined in recent years, this intervention may have helped to maintain students' performance to a level comparable to that of previous years. The outcome of self-assessment online tests indicates that though Mathematics anxiety is lower than during examinations, the poor results obtained for questions requiring mathematical skills are, at least in part, due to a lack of self-efficacy

Affordable Exploration of Mars: Recommendations from a Community Workshop on Sustainable Initial Human Missions

There is a growing consensus that within two decades initial human missions to Mars are affordable under plausible budget assumptions and with sustained international participation. In response to this idea, a distinguished group of experts from the Mars exploration stakeholder communities attended the "Affording Mars" workshop at George Washington University in December, 2013. Participants reviewed and discussed scenarios for affordable and sustainable human and robotic exploration of Mars, the role of the International Space Station over the coming decade as the essential early step toward humans to Mars, possible "bridge" missions in the 2020s, key capabilities required for affordable initial missions, international partnerships, and a usable definition of affordability and sustainability. We report here the findings, observations, and recommendations that were agreed to at that workshop

Erasure detection of a dual-rail qubit encoded in a double-post superconducting cavity

Qubits with predominantly erasure errors present distinctive advantages for quantum error correction(QEC) and fault tolerant quantum computing. Logical qubits based on dual-rail encoding that exploit erasure detection have been recently proposed in superconducting circuit architectures, either with coupled transmons or cavities. Here, we implement a dual-rail qubit encoded in a compact, double-post superconducting cavity. Using an auxiliary transmon, we perform erasure detection on the dual-rail subspace. We characterize the behaviour of the codespace by a novel method to perform joint-Wigner tomography. This is based on modifying the cross-Kerr interaction between the cavity modes and the transmon. We measure an erasure rate of 3.981 +/- 0.003 (ms)-1 and a residual dephasing error rate up to 0.17 (ms)-1 within the codespace. This strong hierarchy of error rates, together with the compact and hardware-efficient nature of this novel architecture, hold promise in realising QEC schemes with enhanced thresholds and improved scaling

Biosynthesis of Mitochondrial Porin and Insertion into the Outer Mitochondrial Membrane of Neuruspora crassa

Mitochondrial porin, the major protein of the outer mitochondrial membrane is synthesized by free cytoplasmic polysomes. The apparent molecular weight of the porin synthesized in homologous or heterologous cell-free systems is the same as that of the mature porin. Transfer in vitro of mitochondrial porin from the cytosolic fraction into the outer membrane of mitochondria could be demonstrated. Before membrane insertion, mitochondrial porin is highly sensitive to added proteinase; afterwards it is strongly protected. Binding of the precursor form to mitochondria occurs at 4°C and appears to precede insertion into the membrane. Unlike transfer of many precursor proteins into or across the inner mitochondrial membrane, assembly of the porin is not dependent on an electrical potential across the inner membrane