Protein flexibility, not disorder, is intrinsic to molecular recognition.

An 'intrinsically disordered protein' (IDP) is assumed to be unfolded in the cell and perform its biological function in that state. We contend that most intrinsically disordered proteins are in fact proteins waiting for a partner (PWPs), parts of a multi-component complex that do not fold correctly in the absence of other components. Flexibility, not disorder, is an intrinsic property of proteins, exemplified by X-ray structures of many enzymes and protein-protein complexes. Disorder is often observed with purified proteins in vitro and sometimes also in crystals, where it is difficult to distinguish from flexibility. In the crowded environment of the cell, disorder is not compatible with the known mechanisms of protein-protein recognition, and, foremost, with its specificity. The self-assembly of multi-component complexes may, nevertheless, involve the specific recognition of nascent polypeptide chains that are incompletely folded, but then disorder is transient, and it must remain under the control of molecular chaperones and of the quality control apparatus that obviates the toxic effects it can have on the cell

Influence of correlations on molecular recognition

The influence of the patchiness and correlations in the distribution of hydrophobic and polar residues at the interface between two rigid biomolecules on their recognition ability is investigated in idealised coarse-grained lattice models. A general two-stage approach is utilised where an ensemble of probe molecules is designed first and the recognition ability of the probe ensemble is related to the free energy of association with both the target molecule and a different rival molecule in a second step. The influence of correlation effects are investigated using numerical Monte Carlo techniques and mean field methods. Correlations lead to different optimum characteristic lengths of the hydrophobic and polar patches for the mutual design of the two biomolecules on the one hand and their recognition ability in the presence of other molecules on the other hand.Comment: 15 pages, 5 figure

Resampling technique applied to statistics of microsegregation characterization

Characterization of chemical heterogeneities at the dendrite scale is of practical importance for understanding phase transformation either during solidification or during subsequent solid-state treatment. Spot analysis with electron probe is definitely well-suited to investigate such heterogeneities at the micron scale that is relevant for most solidified products. However, very few has been done about the statistics of experimental solute distributions gained from such analyses when they are now more and more used for validating simulation data. There are two main sources generating discrepancies between estimated and actual solute distributions in an alloy: i) data sampling with a limited number of measurements to keep analysis within a reasonable time length; and ii) uncertainty linked to the measurement process, namely the physical noise that accompanies X-ray emission. Focusing on the first of these sources, a few 2-D composition images have been generated by phase field modelling of a Mg-Al alloy. These images were then used to obtain "true" solute distributions to which to compare coarse grid analyses as generally performed with a microanalyser. Resampling, i.e. generating several distributions by grid analyses with limited number of picked-up values, was then used to get statistics of estimates of solute distribution. The discussion of the present results deals first with estimating the average solute content and then focuses on the distribution in the primary phase

Influence of Heat Treatment on the Degradation Behaviour of Degradable Magnesium Based Implants

Aim of the study was to characterise the influence of heat treatment on the degradation behaviour and stability of degradable magnesium based implants. For this purpose two groups (untreated/ heat treated) of LAE442 pins were separately analysed in an in vitro and in vivo study. The corrosion behaviour was evaluated during 8 weeks degradation in SBF (in vitro) and 48 weeks degradation intramedullary in the rabbit tibia (in vivo). The analyses were made by using μ-computed tomography and three-point-bending tests. Heat treatment led to altered mechanical and corrosion properties of LAE442.While the initial stability declined significantly a reduction of the degradation rate over either in vitro and in vivo evaluation period is determined. If these alterations are still reasonable for osteosynthesis implants remains to be investigated in further projects.DFG/SFB/59

Embedding finite and infinite words into overlapping tiles

International audienceIn this paper, we study languages of finite and infinite birooted words. We show how the embedding of free ω-semigroups of finite and infinite words into the monoid of birooted words can be generalized to the embedding of two-sorted ω-semigroups into (some notion of) one- sorted ordered ω-monoids. This leads to an algebraic characterization of regular languages of finite and infinite birooted words that generalizes and unifies the known algebraic characterizations of regular languages of finite and infinite words

Walking automata in free inverse monoids

International audienceWalking automata, be they running over words, trees or even graphs, possibly extended with pebbles that can be dropped and lifted on vertices, have long been defined and studied in Computer Science. However, questions concerning walking automata are surprisingly complex to solve. In this paper, we study a generic notion of walking automata over graphs whose semantics naturally lays within inverse semigroup theory. Then, from the simplest notion of walking automata on birooted trees, that is, elements of free inverse monoids, to the more general cases of walking automata on birooted finite subgraphs of Cayley's graphs of groups, that is, elements of free E-unitary inverse monoids, we provide a robust algebraic framework in which various classes of recognizable or regular languages of birooted graphs can uniformly be defined and related one with the other

Optimising the management of vaginal discharge syndrome in Bulgaria: cost effectiveness of four clinical algorithms with risk assessment

OBJECTIVES: To evaluate the performance and cost effectiveness of the WHO recommendations of incorporating risk-assessment scores and population prevalence of Neisseria gonorrhoeae (NG) and Chlamydia trachomatis (CT) into vaginal discharge syndrome (VDS) algorithms. METHODS: Non-pregnant women presenting with VDS were recruited at a non-governmental sexual health clinic in Sofia, Bulgaria. NG and CT were diagnosed by PCR and vaginal infections by microscopy. Risk factors for NG/CT were identified in multivariable analysis. Four algorithms based on different combinations of behavioural factors, clinical findings and vaginal microscopy were developed. Performance of each algorithm was evaluated for detecting vaginal and cervical infections separately. Cost effectiveness was based on cost per patient treated and cost per case correctly treated. Sensitivity analysis explored the influence of NG/CT prevalence on cost effectiveness. RESULTS: 60% (252/420) of women had genital infections, with 9.5% (40/423) having NG/CT. Factors associated with NG/CT included new and multiple sexual partners in the past 3 months, symptomatic partner, childlessness and >or=10 polymorphonuclear cells per field on vaginal microscopy. For NG/CT detection, the algorithm that relied solely on behavioural risk factors was less sensitive but more specific than those that included speculum examination or microscopy but had higher correct-treatment rate and lower over-treatment rates. The cost per true case treated using a combination of risk factors, speculum examination and microscopy was euro 24.08. A halving and tripling of NG/CT prevalence would have approximately the inverse impact on the cost-effectiveness estimates. CONCLUSIONS: Management of NG/CT in Bulgaria was improved by the use of a syndromic approach that included risk scores. Approaches that did not rely on microscopy lost sensitivity but were more cost effective