Properties of Cooperatively Induced Phases in Sensing Models

A large number of eukaryotic cells are able to directly detect external chemical gradients with great accuracy and the ultimate limit to their sensitivity has been a topic of debate for many years. Previous work has been done to understand many aspects of this process but little attention has been paid to the possibility of emergent sensing states. Here we examine how cooperation between sensors existing in a two dimensional network, as they do on the cell's surface, can both enhance and fundamentally alter the response of the cell to a spatially varying signal. We show that weakly interacting sensors linearly amplify the sensors response to an external gradient while a network of strongly interacting sensors form a collective non-linear response with two separate domains of active and inactive sensors forming what have called a "1/2-state" . In our analysis we examine the cell's ability to sense the direction of a signal and pay special attention to the substantially different behavior realized in the strongly interacting regime.Comment: 8 pages, 5 figure

Balanced Ero1 activation and inactivation establishes ER redox homeostasis

The endoplasmic reticulum (ER) provides an environment optimized for oxidative protein folding through the action of Ero1p, which generates disulfide bonds, and Pdi1p, which receives disulfide bonds from Ero1p and transfers them to substrate proteins. Feedback regulation of Ero1p through reduction and oxidation of regulatory bonds within Ero1p is essential for maintaining the proper redox balance in the ER. In this paper, we show that Pdi1p is the key regulator of Ero1p activity. Reduced Pdi1p resulted in the activation of Ero1p by direct reduction of Ero1p regulatory bonds. Conversely, upon depletion of thiol substrates and accumulation of oxidized Pdi1p, Ero1p was inactivated by both autonomous oxidation and Pdi1p-mediated oxidation of Ero1p regulatory bonds. Pdi1p responded to the availability of free thiols and the relative levels of reduced and oxidized glutathione in the ER to control Ero1p activity and ensure that cells generate the minimum number of disulfide bonds needed for efficient oxidative protein folding.National Institutes of Health (U.S.) (GM46941

Non-Fermi Liquid Quantum Impurity Physics from non-Abelian Quantum Hall States

We study the physics of electron tunneling between multiple quantum dots and the edge of a quantum Hall state. Our results generalize earlier work [G. A. Fiete, W. Bishara, C. Nayak, Phys. Rev. Lett. 101, 176801 (2008)] in which it was shown that a single quantum dot tunnel coupled to a non-Abelian quantum Hall state can realize a stable multi-channel Kondo fixed point at low-energy. In this work, we investigate the physics of multiple dots and find that a rich set of possible low-energy fixed points arises, including those with non-Fermi liquid properties. Previously unidentified fixed points may also be among the possibilities. We examine both the situation where the dots are spatially separated and where they are in close proximity. We discuss the relation to previous work on two-impurity Kondo models in Fermi liquids and highlight new research directions in multiple quantum impurity problems.Comment: 12 pages, 2 figure

Redox signaling via the molecular chaperone BiP protects cells against endoplasmic reticulum-derived oxidative stress

Oxidative protein folding in the endoplasmic reticulum (ER) has emerged as a potentially significant source of cellular reactive oxygen species (ROS). Recent studies suggest that levels of ROS generated as a byproduct of oxidative folding rival those produced by mitochondrial respiration. Mechanisms that protect cells against oxidant accumulation within the ER have begun to be elucidated yet many questions still remain regarding how cells prevent oxidant-induced damage from ER folding events. Here we report a new role for a central well-characterized player in ER homeostasis as a direct sensor of ER redox imbalance. Specifically we show that a conserved cysteine in the lumenal chaperone BiP is susceptible to oxidation by peroxide, and we demonstrate that oxidation of this conserved cysteine disrupts BiP's ATPase cycle. We propose that alteration of BiP activity upon oxidation helps cells cope with disruption to oxidative folding within the ER during oxidative stress.Cornell UniversityNational Institutes of Health (U.S.) (Grant GM46941

The interstellar oxygen-K absorption edge as observed by XMM-Newton

High resolution X-ray spectra of the Reflection Grating Spectrometer (RGS) on board the XMM satellite are used to resolve the oxygen K absorption edge. By combining spectra of low and high extinction sources, the observed absorption edge can be split in the true interstellar (ISM) extinction and the instrumental absorption. The detailed ISM edge structure closely follows the edge structure of neutral oxygen as derived by theoretical R-matrix calculations. However, the position of the theoretical edge requires a wavelength shift. In addition the detailed instrumental RGS absorption edge structure is presented. All results are verified by comparing to a subset of Chandra LETG-HRC observations.Comment: LaTeX2e A&A style, 10 pages, 12 postscript figures, accepted for publication in Astronomy and Astrophysic

The relationship between anxiety and acute mountain sickness.

INTRODUCTION: Whilst the link between physical factors and risk of high altitude (HA)-related illness and acute mountain sickness (AMS) have been extensively explored, the influence of psychological factors has been less well examined. In this study we aimed to investigate the relationship between 'anxiety and AMS risk during a progressive ascent to very HA. METHODS: Eighty health adults were assessed at baseline (848m) and over 9 consecutive altitudes during a progressive trek to 5140m. HA-related symptoms (Lake Louise [LLS] and AMS-C Scores) and state anxiety (State-Trait-Anxiety-Score [STAI Y-1]) were examined at each altitude with trait anxiety (STAI Y-2) at baseline. RESULTS: The average age was 32.1 ± 8.3 years (67.5% men). STAI Y-1 scores fell from 848m to 3619m, before increasing to above baseline scores (848m) at ≥4072m (p = 0.01). STAI Y-1 scores correlated with LLS (r = 0.31; 0.24-0.3; P<0.0001) and AMS-C Scores (r = 0.29; 0.22-0.35; P<0.0001). There was significant main effect for sex (higher STAI Y-1 scores in women) and altitude with no sex-x-altitude interaction on STAI Y-1 Scores. Independent predictors of significant state anxiety included female sex, lower age, higher heart rate and increasing LLS and AMS-C scores (p<0.0001). A total of 38/80 subjects (47.5%) developed AMS which was mild in 20 (25%) and severe in 18 (22.5%). Baseline STAI Y-2 scores were an independent predictor of future severe AMS (B = 1.13; 1.009-1.28; p = 0.04; r2 = 0.23) and STAI Y-1 scores at HA independently predicted AMS and its severity. CONCLUSION: Trait anxiety at low altitude was an independent predictor of future severe AMS development at HA. State anxiety at HA was independently associated with AMS and its severity

On the reliability of the theoretical internal conversion coefficients

Possible sources of uncertainties in the calculations of the internal conversion coefficients are studied. The uncertainties induced by them are estimated.Comment: 16 pages (including 3 figures inserted by 'epsfig' macro

Oxidative protein folding by an endoplasmic reticulum-localized peroxiredoxin

Endoplasmic reticulum (ER) oxidation 1 (ERO1) transfers disulfides to protein disulfide isomerase (PDI) and is essential for oxidative protein folding in simple eukaryotes such as yeast and worms. Surprisingly, ERO1-deficient mammalian cells exhibit only a modest delay in disulfide bond formation. To identify ERO1-independent pathways to disulfide bond formation, we purified PDI oxidants with a trapping mutant of PDI. Peroxiredoxin IV (PRDX4) stood out in this list, as the related cytosolic peroxiredoxins are known to form disulfides in the presence of hydroperoxides. Mouse embryo fibroblasts lacking ERO1 were intolerant of PRDX4 knockdown. Introduction of wild-type mammalian PRDX4 into the ER rescued the temperature-sensitive phenotype of an ero1 yeast mutation. In the presence of an H2O2-generating system, purified PRDX4 oxidized PDI and reconstituted oxidative folding of RNase A. These observations implicate ER-localized PRDX4 in a previously unanticipated, parallel, ERO1-independent pathway that couples hydroperoxide production to oxidative protein folding in mammalian cells.EMBO [ALTF649-2008]; Fundacao para a Ciencia e Tecnologia, Portugal [SFRH/BSAB/922/2009, PTDC/QUI/73027/2006, IBB/CBME LA]; NIH [DK47119, DK075311, ES08681]; 100 Women In Hedge Funds Foundation; [NS050276]; [CA016087]; Medical Research Council [G0600717B]info:eu-repo/semantics/publishedVersio

Structural design of the DIII-D radiative divertor

The divertor of the DIII-D tokamak is being modified to operate as a slot type, dissipative divertor. This modification, called the Radiative Divertor Program (RDP) is being carried out in two phases. The design and analysis is complete and hardware is being fabricated for the first phase. This first phase consists of an upper divertor baffle and cryopump to provide some density control for high triangularity, single or double null discharges. Installation of the first phase is scheduled to start in October, 1996. The second phase provides pumping at all four divertor strike points of double null high triangularity discharges and baffling of the neutral particles from transport back to the core plasma. Studies of the effects of varying the slot length and width of the divertor can be easily accomplished with the design of RDP hardware. Static and dynamic analyses of the baffle structures, new cryopumps, and feedlines were performed during the preliminary and final design phases. Disruption loads and differential thermal displacements must be accommodated in the design of these components. With the full RDP hardware installed, the plasma current in DIII-D will be a maximum of 3.0 MA. Plasma disruptions induce toroidal currents in the cryopump, producing complex dynamic loads. Simultaneously, the vacuum vessel vibrations impose a sinusoidal base excitation to the supports for the cryopump. Static and dynamic analyses of the cryopump demonstrate that the stresses due to disruption and thermal loadings satisfy the stress and deflection criteria