Functional specialization of the yeast Rho1 GTP exchange factors

Rho GTPases are regulated in complex spatiotemporal patterns that may be dependent, in part at least, on the multiplicity of their GTP exchange factors (GEFs). Here, we examine the extent of and basis for functional specialization of the Rom2 and Tus1 GEFs that activate the yeast Rho1 GTPase, the ortholog of mammalian RhoA. First, we find that these GEFs selectively activate different Rho1-effector branches. Second, the synthetic genetic networks around ROM2 and TUS1 confirm very different global in vivo roles for these GEFs. Third, the GEFs are not functionally interchangeable: Tus1 cannot replace the essential role of Rom2, even when overexpressed. Fourth, we find that Rom2 and Tus1 localize differently: Rom2 to the growing bud surface and to the bud neck at cytokinesis; Tus1 only to the bud neck but in a distinct pattern. Finally, we find that these GEFs are dependent on different protein co-factors: Rom2 function and localization is largely dependent on Ack1, a SEL1 domain containing protein; Tus1 function and localization is largely dependent on the Tus1-interacting protein Ypl066w (which we name Rgl1). We have revealed a surprising level of diversity among the Rho1 GEFs that contributes another level of complexity to the spatiotemporal control of Rho1

Does gravity cause load-bearing bridges in colloidal and granular systems?

We study structures which can bear loads, "bridges", in particulate packings. To investigate the relationship between bridges and gravity, we experimentally determine bridge statistics in colloidal packings. We vary the effective magnitude and direction of gravity, volume fraction, and interactions, and find that the bridge size distributions depend only on the mean number of neighbors. We identify a universal distribution, in agreement with simulation results for granulars, suggesting that applied loads merely exploit preexisting bridges, which are inherent in dense packings

Degenerations of LeBrun twistor spaces

We investigate various limits of the twistor spaces associated to the self-dual metrics on n CP ^2, the connected sum of the complex projective planes, constructed by C. LeBrun. In particular, we explicitly present the following 3 kinds of degenerations whose limits of the metrics are: (a) LeBrun metrics on (n-1) CP ^2$, (b) (Another) LeBrun metrics on the total space of the line bundle O(-n) over CP ^1 (c) The hyper-Kaehler metrics on the small resolution of rational double points of type A_{n-1}, constructed by Gibbons and Hawking.Comment: 21 pages, 7 figures. V2: A new section added at the end of the article. V3: Reference slightly update

Randomized crossover comparison of proportional assist ventilation and patient-triggered ventilation in extremely low birth weight infants with evolving chronic lung disease

Background: Refinement of ventilatory techniques remains a challenge given the persistence of chronic lung disease of preterm infants. Objective: To test the hypothesis that proportional assist ventilation ( PAV) will allow to lower the ventilator pressure at equivalent fractions of inspiratory oxygen (FiO(2)) and arterial hemoglobin oxygen saturation in ventilator-dependent extremely low birth weight infants in comparison with standard patient-triggered ventilation ( PTV). Methods: Design: Randomized crossover design. Setting: Two level-3 university perinatal centers. Patients: 22 infants ( mean (SD): birth weight, 705 g ( 215); gestational age, 25.6 weeks ( 2.0); age at study, 22.9 days ( 15.6)). Interventions: One 4- hour period of PAV was applied on each of 2 consecutive days and compared with epochs of standard PTV. Results: Mean airway pressure was 5.64 ( SD, 0.81) cm H2O during PAV and 6.59 ( SD, 1.26) cm H2O during PTV ( p < 0.0001), the mean peak inspiratory pressure was 10.3 ( SD, 2.48) cm H2O and 15.1 ( SD, 3.64) cm H2O ( p < 0.001), respectively. The FiO(2) ( 0.34 (0.13) vs. 0.34 ( 0.14)) and pulse oximetry readings were not significantly different. The incidence of arterial oxygen desaturations was not different ( 3.48 ( 3.2) vs. 3.34 ( 3.0) episodes/ h) but desaturations lasted longer during PAV ( 2.60 ( 2.8) vs. 1.85 ( 2.2) min of desaturation/ h, p = 0.049). PaCO2 measured transcutaneously in a subgroup of 12 infants was similar. One infant met prespecified PAV failure criteria. No adverse events occurred during the 164 cumulative hours of PAV application. Conclusions: PAV safely maintains gas exchange at lower mean airway pressures compared with PTV without adverse effects in this population. Backup conventional ventilation breaths must be provided to prevent apnea-related desaturations. Copyright (c) 2007 S. Karger AG, Base

Unsteady flow and particle migration in dense, non-Brown suspensions

We present experimental results on dense corn-starch suspensions as examples of non-Brownian, nearly-hard particles that undergo continuous and discontinuous shear thickening (CST and DST) at intermediate and high densities respectively. Our results offer strong support for recent theories involving a stress-dependent effective contact friction among particles. We show however that in the DST regime, where theory might lead one to expect steady-state shear bands oriented layerwise along the vorticity axis, the real flow is unsteady. To explain this, we argue that steady-state banding is generically ruled out by the requirement that, for hard non-Brownian particles, the solvent pressure and the normal-normal component of the particle stress must balance separately across the interface between bands. (Otherwise there is an unbalanced migration flux.) However, long-lived transient shear bands remain possible.EPSRC (EP/J007404)This is the author accepted manuscript. It is currently under an indefinite embargo pending publication by AIP

Leaf segmentation and tracking using probabilistic parametric active contours

Active contours or snakes are widely used for segmentation and tracking. These techniques require the minimization of an energy function, which is generally a linear combination of a data fit term and a regularization term. This energy function can be adjusted to exploit the intrinsic object and image features. This can be done by changing the weighting parameters of the data fit and regularization term. There is, however, no rule to set these parameters optimally for a given application. This results in trial and error parameter estimation. In this paper, we propose a new active contour framework defined using probability theory. With this new technique there is no need for ad hoc parameter setting, since it uses probability distributions, which can be learned from a given training dataset

Enhancement of oligomeric stability by covalent linkage and its application to the human p53tet domain: thermodynamics and biological implications

Abstract The formation of oligomeric proteins proceeds at a major cost of reducing the translational and rotational entropy for their subunits in order to form the stabilizing interactions found in the oligomeric state. Unlike site-directed mutations, covalent linkage of subunits represents a generically applicable strategy for enhancing oligomeric stability by reducing the entropic driving force for dissociation. Although this can be realized by introducing de novo disulfide cross-links between subunits, issues with irreversible aggregation limit the utility of this approach. In contrast, tandem linkage of subunits in a single polypeptide chain offers a universal method of pre-paying the entropic cost of oligomer formation. In the present paper, thermodynamic, structural and experimental aspects of designing and characterizing tandem-linked oligomers are discussed with reference to engineering a stabilized tetramer of the oligomerization domain of the human p53 tumour-suppressor protein by tandem dimerization

β\beta-Decay Spectrum, Response Function and Statistical Model for Neutrino Mass Measurements with the KATRIN Experiment

The objective of the Karlsruhe Tritium Neutrino (KATRIN) experiment is to determine the effective electron neutrino mass $m(\nu_\text{e})$ with an unprecedented sensitivity of $0.2\,\text{eV}$ (90\% C.L.) by precision electron spectroscopy close to the endpoint of the $\beta$ decay of tritium. We present a consistent theoretical description of the $\beta$ electron energy spectrum in the endpoint region, an accurate model of the apparatus response function, and the statistical approaches suited to interpret and analyze tritium $\beta$ decay data observed with KATRIN with the envisaged precision. In addition to providing detailed analytical expressions for all formulae used in the presented model framework with the necessary detail of derivation, we discuss and quantify the impact of theoretical and experimental corrections on the measured $m(\nu_\text{e})$. Finally, we outline the statistical methods for parameter inference and the construction of confidence intervals that are appropriate for a neutrino mass measurement with KATRIN. In this context, we briefly discuss the choice of the $\beta$ energy analysis interval and the distribution of measuring time within that range.Comment: 27 pages, 22 figures, 2 table

Potentials for hyper-Kahler metrics with torsion

We prove that locally any hyper-K\"ahler metric with torsion admits an HKT potential.Comment: 9 page