De-DUFing the DUFs: Deciphering distant evolutionary relationships of Domains of Unknown Function using sensitive homology detection methods

Background: In the post-genomic era where sequences are being determined at a rapid rate, we are highly reliant on computational methods for their tentative biochemical characterization. The Pfam database currently contains 3,786 families corresponding to ``Domains of Unknown Function'' (DUF) or ``Uncharacterized Protein Family'' (UPF), of which 3,087 families have no reported three-dimensional structure, constituting almost one-fourth of the known protein families in search for both structure and function. Results: We applied a `computational structural genomics' approach using five state-of-the-art remote similarity detection methods to detect the relationship between uncharacterized DUFs and domain families of known structures. The association with a structural domain family could serve as a start point in elucidating the function of a DUF. Amongst these five methods, searches in SCOP-NrichD database have been applied for the first time. Predictions were classified into high, medium and low-confidence based on the consensus of results from various approaches and also annotated with enzyme and Gene ontology terms. 614 uncharacterized DUFs could be associated with a known structural domain, of which high confidence predictions, involving at least four methods, were made for 54 families. These structure-function relationships for the 614 DUF families can be accessed on-line at http://proline.biochem.iisc.ernet.in/RHD_DUFS/. For potential enzymes in this set, we assessed their compatibility with the associated fold and performed detailed structural and functional annotation by examining alignments and extent of conservation of functional residues. Detailed discussion is provided for interesting assignments for DUF3050, DUF1636, DUF1572, DUF2092 and DUF659. Conclusions: This study provides insights into the structure and potential function for nearly 20 % of the DUFs. Use of different computational approaches enables us to reliably recognize distant relationships, especially when they converge to a common assignment because the methods are often complementary. We observe that while pointers to the structural domain can offer the right clues to the function of a protein, recognition of its precise functional role is still `non-trivial' with many DUF domains conserving only some of the critical residues. It is not clear whether these are functional vestiges or instances involving alternate substrates and interacting partners. Reviewers: This article was reviewed by Drs Eugene Koonin, Frank Eisenhaber and Srikrishna Subramanian.

DETERMINATION OF THE MASS OF IGR J17091-3624 FROM ``SPECTRO-TEMPORAL'' VARIATIONS DURING THE ONSET PHASE OF THE 2011 OUTBURST

The 2011 outburst of the black hole candidate IGR J17091-3624 followed the canonical track of state transitions along with the evolution of quasi-periodic oscillation (QPO) frequencies before it began exhibiting various variability classes similar to GRS 1915+105. We use this canonical evolution of spectral and temporal properties to determine the mass of IGR J17091-3624, using three different methods: photon index (Gamma)-QPO frequency (nu) correlation, QPO frequency (nu)-time (day) evolution, and broadband spectral modeling based on two-component advective flow (TCAF). We provide a combined mass estimate for the source using a naive Bayes based joint likelihood approach. This gives a probable mass range of 11.8 M-circle dot-13.7 M-circle dot. Considering each individual estimate and taking the lowermost and uppermost bounds among all three methods, we get a mass range of 8.7 M-circle dot-15.6 M-circle dot with 90% confidence. We discuss the possible implications of our findings in the context of two-component accretion flow.

A posteriori error estimates of discontinuous Galerkin methods for the Signorini problem

A reliable and efficient a posteriori error estimator is derived for a class of discontinuous Galerkin (DG) methods for the Signorini problem. A common property shared by many DG methods leads to a unified error analysis with the help of a constraint preserving enriching map. The error estimator of DG methods is comparable with the error estimator of the conforming methods. Numerical experiments illustrate the performance of the error estimator. (C) 2015 Elsevier B.V. All rights reserved.

Bearing capacity of circular footings over rock mass by using axisymmetric quasi lower bound finite element limit analysis

The ultimate bearing capacity of a circular footing, placed over rock mass, is evaluated by using the lower bound theorem of the limit analysis in conjunction with finite elements and nonlinear optimization. The generalized Hoek-Brown (HB) failure criterion, but by keeping a constant value of the exponent, alpha = 0.5, was used. The failure criterion was smoothened both in the meridian and pi planes. The nonlinear optimization was carried out by employing an interior point method based on the logarithmic barrier function. The results for the obtained bearing capacity were presented in a non-dimensional form for different values of GSI, m(i), sigma(ci)/(gamma b) and q/sigma(ci). Failure patterns were also examined for a few cases. For validating the results, computations were also performed for a strip footing as well. The results obtained from the analysis compare well with the data reported in literature. Since the equilibrium conditions are precisely satisfied only at the centroids of the elements, not everywhere in the domain, the obtained lower bound solution will be approximate not true. (C) 2015 Elsevier Ltd. All rights reserved.

A FRAMEWORK FOR THE ERROR ANALYSIS OF DISCONTINUOUS FINITE ELEMENT METHODS FOR ELLIPTIC OPTIMAL CONTROL PROBLEMS AND APPLICATIONS TO C-0 IP METHODS

In this article, an abstract framework for the error analysis of discontinuous Galerkin methods for control constrained optimal control problems is developed. The analysis establishes the best approximation result from a priori analysis point of view and delivers a reliable and efficient a posteriori error estimator. The results are applicable to a variety of problems just under the minimal regularity possessed by the well-posedness of the problem. Subsequently, the applications of C-0 interior penalty methods for a boundary control problem as well as a distributed control problem governed by the biharmonic equation subject to simply supported boundary conditions are discussed through the abstract analysis. Numerical experiments illustrate the theoretical findings.

Quasi-geostrophic dynamics in the presence of moisture gradients

The derivation of a quasi-geostrophic system from the rotating shallow-water equations on a midlatitude -plane coupled with moisture is presented. Condensation is prescribed to occur whenever the moisture at a point exceeds a prescribed saturation value. It is seen that a slow condensation time-scale is required to obtain a consistent set of equations at leading order. Further, since the advecting wind fields are geostrophic, changes in moisture (and hence precipitation) occur only via non-divergent mechanisms. Following observations, a saturation profile with gradients in the zonal and meridional directions is prescribed. A purely meridional gradient has the effect of slowing down the dry Rossby waves, through a reduction in the equivalent gradient' of the background potential vorticity. A large-scale unstable moist mode results on the inclusion of a zonal gradient by itself, or in conjunction with a meridional moisture gradient. For gradients that are are representative of the atmosphere, the most unstable moist mode propagates zonally in the direction of increasing moisture, matures over an intraseasonal time-scale and has small phase speed.

Reply to Discussion on ``Bearing capacity of circular footings over rock mass by using axisymmetric quasi lower bound finite element limit analysis'' Comput. Geotech. 70 (2015) 138-149]

A discussion has been provided for the comments raised by the discusser (Clausen, 2015)1] on the article recently published by the authors (Chakraborty and Kumar, 2015). The effect of exponent alpha for values of GSI approximately smaller than 30 becomes more critical. On the other hand, for greater values of GSI, the results obtained by the authors earlier remain primarily independent of alpha and can be easily used. (C) 2015 Elsevier Ltd. All rights reserved.

On the Geometrically Dependent Quasi-Saturation and g(m) Reduction in Advanced DeMOS Transistors

This paper reveals an early quasi-saturation (QS) effect attributed to the geometrical parameters in shallow trench isolation-type drain-extended MOS (STI-DeMOS) transistors in advanced CMOS technologies. The quasi-saturation effect leads to serious g(m) reduction in STI-DeMOS. This paper investigates the nonlinear resistive behavior of the drain-extended region and its impact on the particular behavior of the STI-DeMOS transistor. In difference to vertical DMOS or lateral DMOS structures, STI-DeMOS exhibits three distinct regions of the drain extension. A complete understanding of the physics in these regions and their impact on the QS behavior are developed in this paper. An optimization strategy is shown for an improved g(m) device in a state-of-the-art 28-nm CMOS technology node.