Mean first passage time analysis reveals rate-limiting steps, parallel pathways and dead ends in a simple model of protein folding

We have analyzed dynamics on the complex free energy landscape of protein folding in the FOLD-X model, by calculating for each state of the system the mean first passage time to the folded state. The resulting kinetic map of the folding process shows that it proceeds in jumps between well-defined, local free energy minima. Closer analysis of the different local minima allows us to reveal secondary, parallel pathways as well as dead ends.Comment: 7 page

Geometric and analytic views in existence theorems for optimal control. III. Weak solutions

Existence theorems are proved for weak optimal solutions of problems of optimization with distributed and boundary control. Many examples are given. Application is made of recent remarks on closure properties of linear and nonlinear operators. Recent geometric, topological, and analytical views are brought to bear on the underlying seminormality conditions.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/45209/1/10957_2004_Article_BF00934060.pd

Geometric and analytic views in existence theorems for optimal control. II. Distributed and boundary controls

Existence theorems are proved for Lagrange problems of optimization in a given domain G with possibly unbounded distributed controls in G and on the boundary of G , and with functional relations on G and on the boundary represented by closed operators, not necessarily linear. The case where the functional relations are partial differential equations is emphasized. Recent work concerning the reduction or elimination of seminormality requirements is taken into account. Many examples are given.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/45200/1/10957_2004_Article_BF00933208.pd

Reverse wedge osteotomy of the distal radius in Madelung's deformity

Madelung\u27s deformity results from a growth defect in the palmar and ulnar region of the distal radius. It presents as an excessively inclined radial joint surface, inducing "spontaneous progressive palmar subluxation of the wrist". The principle of reverse wedge osteotomy (RWO) consists in the reorientation of the radial joint surface by taking a circumferential bone wedge, the base of which is harvested from the excess of the radial and dorsal cortical bone of the distal radius, then turning it over and putting back this reverse wedge into the osteotomy so as to obtain closure on the excess and opening on the deficient cortical bone. RWO corrects the palmar subluxation of the carpus and improves distal radio-ulnar alignment. All five bilaterally operated patients were satisfied, esthetically and functionally. Its corrective power gives RWO a place apart among the surgical techniques currently available in Madelung\u27s deformity

General behaviour of Bianchi VI_0 solutions with an exponential-potential scalar field

The solutions to the Einstein-Klein-Gordon equations without a cosmological constant are investigated for an exponential potential in a Bianchi VI_0 metric. There exists a two-parameter family of solutions which have a power-law inflationary behaviour when the exponent of the potential, k, satisfies k^2<2. In addition, there exists a two-parameter family of singular solutions for all k^2 values. A simple anisotropic exact solution is found to be stable when 2<k^2.Comment: 10 pages, no figures. To be published in General Relativity and Gravitatio

Stability of inflationary solutions driven by a changing dissipative fluid

In this paper the second Lyapunov method is used to study the stability of the de Sitter phase of cosmic expansion when the source of the gravitational field is a viscous fluid. Different inflationary scenarios related with reheating and decay of mini-blackholes into radiation are investigated using an effective fluid described by time--varying thermodynamical quantities.Comment: 17 pages, LaTeX 2.09, 2 figures. To be published in Classical and Quantum Gravit

Effects of periodic breathing on sleep at high altitude: a randomized, placebo-controlled, crossover study using inspiratory CO2

Abstract: Hypoxia at high altitude facilitates changes in ventilatory control that can lead to nocturnal periodic breathing (nPB). Here, we introduce a placebo-controlled approach to prevent nPB by increasing inspiratory CO2 and used it to assess whether nPB contributes to the adverse effects of hypoxia on sleep architecture. In a randomized, single-blinded, crossover design, 12 men underwent two sojourns (three days/nights each, separated by 4 weeks) in hypobaric hypoxia corresponding to 4000 m altitude, with polysomnography during the first and third night of each sojourn. During all nights, subjects’ heads were encompassed by a canopy retaining exhaled CO2, and CO2 concentration in the canopy (i.e. inspiratory CO2 concentration) was controlled by adjustment of fresh air inflow. Throughout the placebo sojourn inspiratory CO2 was ≤0.2%, whereas throughout the other sojourn it was increased to 1.76% (IQR, 1.07%–2.44%). During the placebo sojourn, total sleep time (TST) with nPB was 54.3% (37.4%–80.8%) and 45.0% (24.5%–56.5%) during the first and the third night, respectively (P = 0.042). Increased inspiratory CO2 reduced TST with nPB by an absolute 38.1% (28.1%–48.1%), the apnoea–hypopnoea index by 58.1/h (40.1–76.1/h), and oxygen desaturation index ≥3% by 56.0/h (38.9.1–73.2/h) (all P < 0.001), whereas it increased the mean arterial oxygen saturation in TST by 2.0% (0.4%–3.5%, P = 0.035). Increased inspiratory CO2 slightly increased the percentage of N3 sleep during the third night (P = 0.045), without other effects on sleep architecture. Increasing inspiratory CO2 effectively prevented hypoxia-induced nPB without affecting sleep macro-architecture, indicating that nPB does not explain the sleep deterioration commonly observed at high altitudes. (Figure presented.). Key points: Periodic breathing is common during sleep at high altitude, and it is unclear how this affects sleep architecture. We developed a placebo-controlled approach to prevent nocturnal periodic breathing (nPB) with inspiratory CO2 administration and used it to assess the effects of nPB on sleep in hypobaric hypoxia. Nocturnal periodic breathing was effectively mitigated by an increased inspiratory CO2 fraction in a blinded manner. Prevention of nPB did not lead to relevant changes in sleep architecture in hypobaric hypoxia. We conclude that nPB does not explain the deterioration in sleep architecture commonly observed at high altitude

Existence theorems for lagrange control problems with unbounded time domain

Existence theorems are proved for usual Lagrange control systems, in which the time domain is unbounded. As usual in Lagrange problems, the cost functional is an improper integral, the state equation is a system of ordinary differential equations, with assigned boundary conditions, and constraints may be imposed on the values of the state and control variables. It is shown that the boundary conditions at infinity require a particular analysis. Problems of this form can be found in econometrics (e.g., infinite-horizon economic models) and operations research (e.g., search problems).Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/45207/1/10957_2004_Article_BF00934054.pd

‘RE/TRS’ is a Girl’s Subject: Talking about Gender and the Discourse of ‘Religion’ in UK Educational Spaces

This article addresses what appears to be a retrenchment into narrower forms of identification and an increased suspicion of difference in the context of educational policy in the UK &ndash; especially in relation to &lsquo;Religious Education&rsquo;. The adoption of standardized management protocols &ndash; &lsquo;managerialism&rsquo; &ndash; across most if not all policy contexts including public educational spaces reduces spaces for encountering or addressing genuine difference and for discovering something new and different. A theory of the &lsquo;feminization of religion&rsquo; associated historically with Barbara Welter, provides some useful insights as to why this might be, suggesting that those in British society who would prefer to see greater separation from &lsquo;religion&rsquo; in &lsquo;secular&rsquo; schools may well also be caught up in forms of gender stereotyping

Heterologous expression screens in Nicotiana benthamiana identify a candidate effector of the wheat Yellow Rust Pathogen that associates with processing bodies

Rust fungal pathogens of wheat (Triticum spp.) affect crop yields worldwide. The molecular mechanisms underlying the virulence of these pathogens remain elusive, due to the limited availability of suitable molecular genetic research tools. Notably, the inability to perform high-throughput analyses of candidate virulence proteins (also known as effectors) impairs progress. We previously established a pipeline for the fast-forward screens of rust fungal candidate effectors in the model plant Nicotiana benthamiana. This pipeline involves selecting candidate effectors in silico and performing cell biology and protein-protein interaction assays in planta to gain insight into the putative functions of candidate effectors. In this study, we used this pipeline to identify and characterize sixteen candidate effectors from the wheat yellow rust fungal pathogen Puccinia striiformis f sp tritici. Nine candidate effectors targeted a specific plant subcellular compartment or protein complex, providing valuable information on their putative functions in plant cells. One candidate effector, PST02549, accumulated in processing bodies (P-bodies), protein complexes involved in mRNA decapping, degradation, and storage. PST02549 also associates with the P-body-resident ENHANCER OF mRNA DECAPPING PROTEIN 4 (EDC4) from N. benthamiana and wheat. We propose that P-bodies are a novel plant cell compartment targeted by pathogen effectors