Minimal distance transformations between links and polymers: Principles and examples

The calculation of Euclidean distance between points is generalized to one-dimensional objects such as strings or polymers. Necessary and sufficient conditions for the minimal transformation between two polymer configurations are derived. Transformations consist of piecewise rotations and translations subject to Weierstrass-Erdmann corner conditions. Numerous examples are given for the special cases of one and two links. The transition to a large number of links is investigated, where the distance converges to the polymer length times the mean root square distance (MRSD) between polymer configurations, assuming curvature and non-crossing constraints can be neglected. Applications of this metric to protein folding are investigated. Potential applications are also discussed for structural alignment problems such as pharmacophore identification, and inverse kinematic problems in motor learning and control.Comment: Submitted to J. Phys.:Condens. Matte

Protein folding rates correlate with heterogeneity of folding mechanism

By observing trends in the folding kinetics of experimental 2-state proteins at their transition midpoints, and by observing trends in the barrier heights of numerous simulations of coarse grained, C-alpha model, Go proteins, we show that folding rates correlate with the degree of heterogeneity in the formation of native contacts. Statistically significant correlations are observed between folding rates and measures of heterogeneity inherent in the native topology, as well as between rates and the variance in the distribution of either experimentally measured or simulated phi-values.Comment: 11 pages, 3 figures, 1 tabl

Evaluating the performance of model transformation styles in Maude

Rule-based programming has been shown to be very successful in many application areas. Two prominent examples are the specification of model transformations in model driven development approaches and the definition of structured operational semantics of formal languages. General rewriting frameworks such as Maude are flexible enough to allow the programmer to adopt and mix various rule styles. The choice between styles can be biased by the programmer’s background. For instance, experts in visual formalisms might prefer graph-rewriting styles, while experts in semantics might prefer structurally inductive rules. This paper evaluates the performance of different rule styles on a significant benchmark taken from the literature on model transformation. Depending on the actual transformation being carried out, our results show that different rule styles can offer drastically different performances. We point out the situations from which each rule style benefits to offer a valuable set of hints for choosing one style over the other

6'-Methoxy Raloxifene-analog enhances mouse bone properties with reduced estrogen receptor binding

Raloxifene (RAL) is an FDA-approved drug used to treat osteoporosis in postmenopausal women. RAL suppresses bone loss primarily through its role as a selective estrogen receptor modulator (SERM). This hormonal estrogen therapy promotes unintended side effects, such as hot flashes and increased thrombosis risk, and prevents the drug from being used in some patient populations at-risk for fracture, including children with bone disorders. It has recently been demonstrated that RAL can have significant positive effects on overall bone mechanical properties by binding to collagen and increasing bone tissue hydration in a cell-independent manner. A Raloxifene-Analog (RAL-A) was synthesized by replacing the 6-hydroxyl substituent with 6-methoxy in effort to reduce the compound's binding affinity for estrogen receptors (ER) while maintaining its collagen-binding ability. It was hypothesized that RAL-A would improve the mechanical integrity of bone in a manner similar to RAL, but with reduced estrogen receptor binding. Molecular assessment showed that while RAL-A did reduce ER binding, downstream ER signaling was not completely abolished. In-vitro, RAL-A performed similarly to RAL and had an identical concentration threshold on osteocyte cell proliferation, differentiation, and function. To assess treatment effect in-vivo, wildtype (WT) and heterozygous (OIM+/-) female mice from the Osteogenesis Imperfecta (OI) murine model were treated with either RAL or RAL-A from 8 weeks to 16 weeks of age. There was an untreated control group for each genotype as well. Bone microarchitecture was assessed using microCT, and mechanical behavior was assessed using 3-point bending. Results indicate that both compounds produced analogous gains in tibial trabecular and cortical microarchitecture. While WT mechanical properties were not drastically altered with either treatment, OIM+/- mechanical properties were significantly enhanced, most notably, in post-yield properties including bone toughness. This proof-of-concept study shows promising results and warrants the exploration of additional analog iterations to further reduce ER binding and improve fracture resistance

Implementing Groundness Analysis with Definite Boolean Functions

The domain of definite Boolean functions, Def, can be used to express the groundness of, and trace grounding dependencies between, program variables in (constraint) logic programs. In this paper, previously unexploited computational properties of Def are utilised to develop an efficient and succinct groundness analyser that can be coded in Prolog. In particular, entailment checking is used to prevent unnecessary least upper bound calculations. It is also demonstrated that join can be defined in terms of other operations, thereby eliminating code and removing the need for preprocessing formulae to a normal form. This saves space and time. Furthermore, the join can be adapted to straightforwardly implement the downward closure operator that arises in set sharing analyses. Experimental results indicate that the new Def implementation gives favourable results in comparison with BDD-based groundness analyses

Leveraging Semantic Web Service Descriptions for Validation by Automated Functional Testing

Recent years have seen the utilisation of Semantic Web Service descriptions for automating a wide range of service-related activities, with a primary focus on service discovery, composition, execution and mediation. An important area which so far has received less attention is service validation, whereby advertised services are proven to conform to required behavioural specifications. This paper proposes a method for validation of service-oriented systems through automated functional testing. The method leverages ontology-based and rule-based descriptions of service inputs, outputs, preconditions and effects (IOPE) for constructing a stateful EFSM specification. The specification is subsequently utilised for functional testing and validation using the proven Stream X-machine (SXM) testing methodology. Complete functional test sets are generated automatically at an abstract level and are then applied to concrete Web services, using test drivers created from the Web service descriptions. The testing method comes with completeness guarantees and provides a strong method for validating the behaviour of Web services

Non-Markovian Configurational Diffusion and Reaction Coordinates for Protein Folding

The non-Markovian nature of polymer motions is accounted for in folding kinetics, using frequency-dependent friction. Folding, like many other problems in the physics of disordered systems, involves barrier crossing on a correlated energy landscape. A variational transition state theory (VTST) that reduces to the usual Bryngelson-Wolynes Kramers approach when the non-Markovian aspects are neglected is used to obtain the rate, without making any assumptions regarding the size of the barrier, or the memory time of the friction. The transformation to collective variables dependent on the dynamics of the system allows the theory to address the controversial issue of what are ``good'' reaction coordinates for folding.Comment: 9 pages RevTeX, 3 eps-figures included, submitted to PR

Dynamical Black Hole Masses of BL Lac Objects from the Sloan Digital Sky Survey

We measure black hole masses for 71 BL Lac objects from the Sloan Digital Sky Survey with redshifts out to z~0.4. We perform spectral decompositions of their nuclei from their host galaxies and measure their stellar velocity dispersions. Black hole masses are then derived from the black hole mass - stellar velocity dispersion relation. We find BL Lac objects host black holes of similar masses, ~10^{8.5} M_sun, with a dispersion of 0.4 dex, similar to the uncertainties on each black hole measurement. Therefore, all BL Lac objects in our sample have the same indistinguishable black hole mass. These 71 BL Lac objects follow the black hole mass - bulge luminosity relation, and their narrow range of host galaxy luminosities confirm previous claims that BL Lac host galaxies can be treated as standard candles. We conclude that the observed diversity in the shapes of BL Lac object spectral energy distributions is not strongly driven by black hole mass or host galaxy properties.Comment: 9 pages, 5 figures, 1 table. Accepted for publication in MNRA