Abstract

Protein domains are minimal structural units that can independently fold and carry out discrete biological functions. Evolutionary divergence amongst proteins not only cause considerable sequence changes of protein domains of similar folds and functions, but can also give rise to remarkable length variations. Rapid and heuristic sequence search algorithms are generally sensitive and effective in recognizing protein domains that are distantly related within large sequence databases, but are not well-suited to identify remote homologues of varying lengths. It is also challenging to distinguish reliable hits from a vast number of putative false positives that could have suboptimal sequence similarities. Here, we present a data-mining approach that provides stage-specific filters in sequence searches to reliably accumulate remote homologues which encourages sampling of length variations albeit no compensation on the validity of hitherto identified distant relationships. Realization of remote homologues with vivid length variations could contribute to better understanding of functional variety within protein domain superfamilies.

Abstract

Advances in sensing and data gathering technologies have resulted in an explosion in the volume of data that is being generated, processed, and archived. In particular, this information overload calls for new methods for querying large spatial datasets, since users are often not interested in merely retrieving a list of all data items satisfying a query, but would, instead, like a more informative \summary" of the retrieved items. An example is the so-called top-k problem, where the goal is to retrieve from a set of n weighted points in IRd the k most signicant points, ranked by their weights, that lie in an orthogonal query box in IRd (rather than get a list of all points lying in the query box). In this paper, ecient and output-sensitive solutions are presented for this problem in two settings. In the rst setting, the k points are reported in arbitrary order and the underlying set can be updated dynamically through insertions and deletions of points. In the second setting, the k points are reported in sorted order of their weights.

Abstract

Hierarchical Ring Networks are widely used in communication systems, logistics and shared multiprocessors. It is hence imperative that efficient design of these structures has to be carried out, to reduce costs of their installation and help increase the ease of management. In this paper, we look at the problem of designing efficient 2- level Hierarchical Ring Networks, in the context of link costs optimization. 2-level HRNs only have two kinds of rings - local rings to connect disjoint sets of nodes and a global ring to interconnect all the local rings. We present an algorithm that is based on Simulated Annealing. We present results for scenarios containing upto 300 nodes. The results obtained from the algorithm are most encouraging.

Abstract

t Tropical islands are special and sensitive ecosystems which are subjected to various disturbances imposed by human activities and natural disasters. A detailed study about the changing landscape scenarios of these fragile island systems induced by various driving factors could be used for setting up measurements in support of conservation and sustainable development projects. The current research is a meta-analysis of the studies carried out in Andaman and Nicobar islands which analyzed the impact of tsunami of 2004 using geospatial tools. Based on the analysis, it was observed that the Nicobar islands were more affected compared to the Andaman islands. The majority of the researchers used preand post-tsunami satellite imagery and adopted visual interpretation method to delineate the changed classes. The study infers uplift of land in Andaman (exposing) and subsidence in Nicobar islands (inundation) with severe damage to the coastal elements like mangroves, coral reefs, plantations and in few cases interior forest. The analysis showed there were no records of the damage for some small islands. Finally, it is concluded that utility of microwave satellite data for change analysis will prove better in regions like Andaman and Nicobar where it is difficult to get cloud free optical data because of the high monsoon periods in these islands. It is also suggested that future work utilizing suitable temporal satellite imagery should focus on the extent of recovery of vegetation and other coastal elements which suffer the impact of disaster.

Abstract

Here, we present an update of the CHARMM27 all-atom additive force field for nucleic acids that improves the treatment of RNA molecules. The original CHARMM27 force field parameters exhibit enhanced Watson-Crick base pair opening which is not consistent with experiment, whereas analysis of molecular dynamics (MD) simulations show the 2'-hydroxyl moiety to almost exclusively sample the O3' orientation. Quantum mechanical (QM) studies of RNA related model compounds indicate the energy minimum associated with the O3' orientation to be too favorable, consistent with the MD results. Optimization of the dihedral parameters dictating the energy of the 2'-hydroxyl proton targeting the QM data yielded several parameter sets, which sample both the base and O3' orientations of the 2'-hydroxyl to varying degrees. Selection of the final dihedral parameters was based on reproduction of hydration behavior as related to a survey of crystallographic data and better agreement with experimental NMR Jcoupling values. Application of the model, designated CHARMM36, to a collection of canonical and noncanonical RNA molecules reveals overall improved agreement with a range of experimental observables as compared to CHARMM27. The results also indicate the sensitivity of the conformational heterogeneity of RNA to the orientation of the 2'-hydroxyl moiety and support a model whereby the 2'- hydroxyl can enhance the probability of conformational transitions in RNA.

Abstract

Background: The extracellular signal-regulated kinase-1 and 2 (ERK1/2) proteins play an important role in cancer cell proliferation and survival. ERK1/2 proteins also are important for normal cell functions. Thus, anti-cancer therapies that block all ERK1/2 signaling may result in undesirable toxicity to normal cells. As an alternative, we have used computational and biological approaches to identify low-molecular weight compounds that have the potential to interact with unique ERK1/2 docking sites and selectively inhibit interactions with substrates involved in promoting cell proliferation. Methods: Colony formation and water soluble tetrazolium salt (WST) assays were used to determine the effects of test compounds on cell proliferation. Changes in phosphorylation and protein expression in response to test compound treatment were examined by immunoblotting and in vitro kinase assays. Apoptosis was determined with immunoblotting and caspase activity assays. Results: In silico modeling was used to identify compounds that were structurally similar to a previously identified parent compound, called 76. From this screen, several compounds, termed 76.2, 76.3, and 76.4 sharing a common thiazolidinedione core with an aminoethyl side group, inhibited proliferation and induced apoptosis of HeLa cells. However, the active compounds were less effective in inhibiting proliferation or inducing apoptosis in non-transformed epithelial cells. Induction of HeLa cell apoptosis appeared to be through intrinsic mechanisms involving caspase-9 activation and decreased phosphorylation of the pro-apoptotic Bad protein. Cell-based and in vitro kinase assays indicated that compounds 76.3 and 76.4 directly inhibited ERK-mediated phosphorylation of caspase-9 and the p90Rsk-1 kinase, which phosphorylates and inhibits Bad, more effectively than the parent compound 76. Further examination of the test compound’s mechanism of action showed little effects on related MAP kinases or other cell survival proteins. Conclusion: These findings support the identification of a class of ERK-targeted molecules that can induce apoptosis in transformed cells by inhibiting ERK-mediated phosphorylation and inactivation of pro-apoptoticproteins.

Abstract

An acyclic vertex coloring of a graph is a proper vertex coloring such that there are no bichromatic cycles. The acyclic chromatic number of G, denoted a (G), is the minimum number of colors required for acyclic vertex coloring of graph G. For a family F of graphs, the acyclic chromatic number of F, denoted by a (F), is defined as the maximum a (G) over all the graphs G∈ F. In this paper we show that a (F)= 8 where F is the family of graphs of maximum degree 5 and give a linear time algorithm to achieve this bound.

Abstract

This paper considers the question of how many colors a distributed graph coloring algorithm would need to use if it had only k rounds available, for any positive integer k. In our main result, we present an algorithm that runs in O(k) rounds for any k bounded below by ©(log log n) and bounded above by O(√log n), and uses O(a Å n1/k) colors to color a graph with arboricity a. This result is optimal since the palette size matches the lower bound of Barenboim and Elkin (PODC 2008). This result is achieved via the use of several new results developed in this paper on coloring graphs whose edges have been acyclically oriented. For example, suppose that G is an n-vertex, acyclically oriented graph with maximum out-degree Δo. We present an algorithm that, for any k ≥ 2 loglog n, runs in O(k) rounds on G to produce an (i) O(Δo)-coloring when Δo Δ ©(maxkn2/k2log1+1/kn, 2k) and an (ii) O(Δo Å n2/k2)-coloring when Δo ∈ Ω(maxk log1+1/kn, 2k). These results are useful in any setting where it is possible to efficiently compute acyclic orientations of a graph with Δo << Δ. We derive non-trivial bounds on the palette size even when k < 2 loglog n. Our main technical contributions can be summarized as: (i) developing a k-round version of the algorithm of Kothapalli et al. (IPDPS 2006) which computes an O(?)-coloring of a graph in O(√log n) rounds, and (ii) developing an oriented version of the Brooks-Vizing coloring result of Grable and Panconesi (SODA 1998).

Abstract

Pneumoconiosis, a lung disease caused by the inhalation of dust, is mainly diagnosed using chest radiographs. The effects of using contralateral symmetric (CS) information present in chest radiographs in the diagnosis of pneumoconiosis are studied using an eye tracking experimental study. The role of expertise and the influence of CS information on the performance of readers with different expertise level are also of interest. Experimental subjects ranging from novices & medical students to staff radiologists were presented with 17 double and 16 single lung images, and were asked to give profusion ratings for each lung zone. Eye movements and the time for their diagnosis were also recorded. Kruskal-Wallis test (χ2(6) = 13.38, p = .038), showed that the observer error (average sum of absolute differences) in double lung images differed significantly across the different expertise categories when considering all the participants. Wilcoxon-signed rank test indicated that the observer error was significantly higher for single-lung images (Z = 3.13, p < .001) than for the double-lung images for all the participants. Mann-Whitney test (U = 28, p = .038) showed that the differential error between single and double lung images is significantly higher in doctors [staff & residents] than in non-doctors [others]. Thus, Expertise & CS information plays a significant role in the diagnosis of pneumoconiosis. CS information helps in diagnosing pneumoconiosis by reducing the general tendency of giving less profusion ratings. Training and experience appear to play important roles in learning to use the CS information present in the chest radiographs.

Abstract

Automatic retinal image analysis is emerging as an important screening tool for early detection of eye diseases. Glaucoma is one of the most common causes of blindness. The manual examination of optic disk (OD) is a standard procedure used for detecting glaucoma. In this paper, we present an automatic OD parameterization technique based on segmented OD and cup regions obtained from monocular retinal images. A novel OD segmentation method is proposed which integrates the local image information around each point of interest in multidimensional feature space to provide robustness against variations found in and around the OD region. We also propose a novel cup segmentation method which is based on anatomical evidence such as vessel bends at the cup boundary, considered relevant by glaucoma experts. Bends in a vessel are robustly detected using a region of support concept, which automatically selects the right scale for analysis. A multi-stage strategy is employed to derive a reliable subset of vessel bends calledr-bends followed by a local spline fitting to derive the desired cup boundary. The method has been evaluated on 138 images comprising 33 normal and 105 glaucomatous images against three glaucoma experts. The obtained segmentation results show consistency in handling various geometric and photometric variations found across the dataset. The estimation error of the method or vertical cup-to-disk diameter ratio is 0.09/0.08 (mean/standard deviation) while for cup-to-disk area ratio it is 0.12/0.10. Overall,the obtained qualitative and quantitative results show effective-ness in both segmentation and subsequent OD parameterization for glaucoma assessment.