DNA Free Energy-Based Promoter Prediction and Comparative Analysis of Arabidopsis and Rice Genomes

The cis-regulatory regions on DNA serve as binding sites for proteins such as transcription factors and RNA polymerase. The combinatorial interaction of these proteins plays a crucial role in transcription initiation, which is an important point of control in the regulation of gene expression. We present here an analysis of the performance of an in silico method for predicting cis-regulatory regions in the plant genomes of Arabidopsis (Arabidopsis thaliana) and rice (Oryza sativa) on the basis of free energy of DNA melting. For protein-coding genes, we achieve recall and precision of 96% and 42% for Arabidopsis and 97% and 31% for rice, respectively. For noncoding RNA genes, the program gives recall and precision of 94% and 75% for Arabidopsis and 95% and 90% for rice, respectively. Moreover, 96% of the false-positive predictions were located in noncoding regions of primary transcripts, out of which 20% were found in the first intron alone, indicating possible regulatory roles. The predictions for orthologous genes from the two genomes showed a good correlation with respect to prediction scores and promoter organization. Comparison of our results with an existing program for promoter prediction in plant genomes indicates that our method shows improved prediction capability.

A new parallel overlapped domain decomposition method for nonlinear dynamic finite element analysis

In this paper a new parallel algorithm for nonlinear transient dynamic analysis of large structures has been presented. An unconditionally stable Newmark-beta method (constant average acceleration technique) has been employed for time integration. The proposed parallel algorithm has been devised within the broad framework of domain decomposition techniques. However, unlike most of the existing parallel algorithms (devised for structural dynamic applications) which are basically derived using nonoverlapped domains, the proposed algorithm uses overlapped domains. The parallel overlapped domain decomposition algorithm proposed in this paper has been formulated by splitting the mass, damping and stiffness matrices arises out of finite element discretisation of a given structure. A predictor-corrector scheme has been formulated for iteratively improving the solution in each step. A computer program based on the proposed algorithm has been developed and implemented with message passing interface as software development environment. PARAM-10000 MIMD parallel computer has been used to evaluate the performances. Numerical experiments have been conducted to validate as well as to evaluate the performance of the proposed parallel algorithm. Comparisons have been made with the conventional nonoverlapped domain decomposition algorithms. Numerical studies indicate that the proposed algorithm is superior in performance to the conventional domain decomposition algorithms. (C) 2003 Elsevier Ltd. All rights reserved.

Scalable Context-Sensitive Points-To Analysis Using Multi-Dimensional Bloom Filters

Context-sensitive points-to analysis is critical for several program optimizations. However, as the number of contexts grows exponentially, storage requirements for the analysis increase tremendously for large programs, making the analysis non-scalable. We propose a scalable flow-insensitive context-sensitive inclusion-based points-to analysis that uses a specially designed multi-dimensional bloom filter to store the points-to information. Two key observations motivate our proposal: (i) points-to information (between pointer-object and between pointer-pointer) is sparse, and (ii) moving from an exact to an approximate representation of points-to information only leads to reduced precision without affecting correctness of the (may-points-to) analysis. By using an approximate representation a multi-dimensional bloom filter can significantly reduce the memory requirements with a probabilistic bound on loss in precision. Experimental evaluation on SPEC 2000 benchmarks and two large open source programs reveals that with an average storage requirement of 4MB, our approach achieves almost the same precision (98.6%) as the exact implementation. By increasing the average memory to 27MB, it achieves precision upto 99.7% for these benchmarks. Using Mod/Ref analysis as the client, we find that the client analysis is not affected that often even when there is some loss of precision in the points-to representation. We find that the NoModRef percentage is within 2% of the exact analysis while requiring 4MB (maximum 15MB) memory and less than 4 minutes on average for the points-to analysis. Another major advantage of our technique is that it allows to trade off precision for memory usage of the analysis.

New Concepts for Three-Dimensional Shape Analysis

A new approach to machine representation and analysis of three-dimensional objects is presented. The representation, based on the notion of "skeleton" of an object leads to a scheme for comparing two given object views for shape relations. The objects are composed of long, thin, rectangular prisms joined at their ends. The input picture to the program is the digitized line drawing portraying the three-dimensional object. To compare two object views, two characteristic vertices called "cardinal point" and "end-cardinal point," occurring consistently at the bends and open ends of the object are detected. The skeletons are then obtained as a connected path passing through these points. The shape relationships between the objects are then obtained from the matching characteristics of their skeletons. The method explores the possibility of a more detailed and finer analysis leading to detection of features like symmetry, asymmetry and other shape properties of an object.

Null Dereference Verification via Over-approximated Weakest Pre-conditions Analysis

Null dereferences are a bane of programming in languages such as Java. In this paper we propose a sound, demand-driven, inter-procedurally context-sensitive dataflow analysis technique to verify a given dereference as safe or potentially unsafe. Our analysis uses an abstract lattice of formulas to find a pre-condition at the entry of the program such that a null-dereference can occur only if the initial state of the program satisfies this pre-condition. We use a simplified domain of formulas, abstracting out integer arithmetic, as well as unbounded access paths due to recursive data structures. For the sake of precision we model aliasing relationships explicitly in our abstract lattice, enable strong updates, and use a limited notion of path sensitivity. For the sake of scalability we prune formulas continually as they get propagated, reducing to true conjuncts that are less likely to be useful in validating or invalidating the formula. We have implemented our approach, and present an evaluation of it on a set of ten real Java programs. Our results show that the set of design features we have incorporated enable the analysis to (a) explore long, inter-procedural paths to verify each dereference, with (b) reasonable accuracy, and (c) very quick response time per dereference, making it suitable for use in desktop development environments.

Frequency response analysis of layered ground in Ahmedabad during Bhuj earthquake

This paper presents the results of seismic response analysis of layered ground in Ahmedabad City during the earthquake in Bhuj on 26(th) January 2001. An attempt has been made to understand the reasons for the failure of multistoreyed buildings founded on soft alluvial deposits in Ahmedabad. Standard Penetration test at a site very close to the Sabarmati river belt was carried out for geotechnical investigations. The program SHAKE91, widely used in the field of earthquake engineering for computing the seismic response of horizontally layered soil deposits, was used to analyse the soil profile at the selected site considering the ground as one dimensional layered elastic system. The ground accelerations recorded at the ground floor of the Regional Passport Staff Quarters building, which is very close to the investigated site, was used as input motion. Also, Finite Element Analysis was carried out for different configurations of multistorey building frames for evaluating their natural frequencies and is compared with the predominant frequency of the layered soil system. The results reveal that the varying degree of damage to multistorey buildings in the close proximity of Sabarmati river area was essentially due to the large amplification of the ground and the near resonance condition.

Damage limit states of reinforced concrete beams subjected to incremental cyclic loading using relaxation ratio analysis of AE parameters

This paper presents an experimental study on damage assessment of reinforced concrete (RC) beams subjected to incremental cyclic loading. During testing acoustic emissions (AEs) were recorded. The analysis of the AE released was carried out by using parameters relaxation ratio, load ratio and calm ratio. Digital image correlation (DIC) technique and tracking with available MATLAB program were used to measure the displacement and surface strains in concrete. Earlier researchers classified the damage in RC beams using Kaiser effect, crack mouth opening displacement and proposed a standard. In general (or in practical situations), multiple cracks occur in reinforced concrete beams. In the present study damage assessment in RC beams was studied according to different limit states specified by the code of practice IS-456:2000 and AE technique. Based on the two ratios namely load ratio and calm ratio and when the deflection reached approximately 85% of the maximum allowable deflection it was observed that the RC beams were heavily damaged. The combination of AE and DIC techniques has the potential to provide the state of damage in RC structures.

Dataflow analysis for data-race free programs

Memory models for shared-memory concurrent programming languages typically guarantee sequential consistency (SC) semantics for datarace-free (DRF) programs, while providing very weak or no guarantees for non-DRF programs. In effect programmers are expected to write only DRF programs, which are then executed with SC semantics. With this in mind, we propose a novel scalable solution for dataflow analysis of concurrent programs, which is proved to be sound for DRF programs with SC semantics. We use the synchronization structure of the program to propagate dataflow information among threads without requiring to consider all interleavings explicitly. Given a dataflow analysis that is sound for sequential programs and meets certain criteria, our technique automatically converts it to an analysis for concurrent programs.

Analysis of distance relay trip regions for EHV and UHV transmission lines

This paper presents comparative evaluation of the distance relay characteristics for UHV and EHV transmission lines. Distance protection relay characteristics for the EHV and UHV systems are developed using Electromagnetic Transients (EMT) program. The variation of ideal trip boundaries for both the systems are presented. Unlike the conventional distance protection relay which uses a lumped parameter model, this paper uses the distributed parameter model. The effect of larger shunt susceptance on the trip boundaries is highlighted. Performance of distance relay with ideal trip boundaries for EHV and UHV lines have been tested for various fault locations and fault resistances. Electromagnetic Transients (EMT) program has been developed considering distributed parameter line model for simulating the test systems. The voltage and current phasors are computed from the signals using an improved full cycle DFT algorithm taking 20 samples per cycle. Two practical transmission systems of Indian power grid, namely 765 kV UHV transmission line and SREB 24-bus 400kV EHV system are used to test the performance of the proposed approach.

Estimation of Probabilistic Bounds on Phase CPI and Relevance in WCET Analysis

Estimating program worst case execution time(WCET) accurately and efficiently is a challenging task. Several programs exhibit phase behavior wherein cycles per instruction (CPI) varies in phases during execution. Recent work has suggested the use of phases in such programs to estimate WCET with minimal instrumentation. However the suggested model uses a function of mean CPI that has no probabilistic guarantees. We propose to use Chebyshev's inequality that can be applied to any arbitrary distribution of CPI samples, to probabilistically bound CPI of a phase. Applying Chebyshev's inequality to phases that exhibit high CPI variation leads to pessimistic upper bounds. We propose a mechanism that refines such phases into sub-phases based on program counter(PC) signatures collected using profiling and also allows the user to control variance of CPI within a sub-phase. We describe a WCET analyzer built on these lines and evaluate it with standard WCET and embedded benchmark suites on two different architectures for three chosen probabilities, p={0.9, 0.95 and 0.99}. For p= 0.99, refinement based on PC signatures alone, reduces average pessimism of WCET estimate by 36%(77%) on Arch1 (Arch2). Compared to Chronos, an open source static WCET analyzer, the average improvement in estimates obtained by refinement is 5%(125%) on Arch1 (Arch2). On limiting variance of CPI within a sub-phase to {50%, 10%, 5% and 1%} of its original value, average accuracy of WCET estimate improves further to {9%, 11%, 12% and 13%} respectively, on Arch1. On Arch2, average accuracy of WCET improves to 159% when CPI variance is limited to 50% of its original value and improvement is marginal beyond that point.

Static analysis for checking data format compatibility of programs

Large software systems are developed by composing multiple programs. If the programs manip-ulate and exchange complex data, such as network packets or files, it is essential to establish that they follow compatible data formats. Most of the complexity of data formats is associated with the headers. In this paper, we address compatibility of programs operating over headers of network packets, files, images, etc. As format specifications are rarely available, we infer the format associated with headers by a program as a set of guarded layouts. In terms of these formats, we define and check compatibility of (a) producer-consumer programs and (b) different versions of producer (or consumer) programs. A compatible producer-consumer pair is free of type mismatches and logical incompatibilities such as the consumer rejecting valid outputs gen-erated by the producer. A backward compatible producer (resp. consumer) is guaranteed to be compatible with consumers (resp. producers) that were compatible with its older version. With our prototype tool, we identified 5 known bugs and 1 potential bug in (a) sender-receiver modules of Linux network drivers of 3 vendors and (b) different versions of a TIFF image library.

DEFINING alpha-HELIX GEOMETRY BY C-alpha ATOM TRACE vs (phi-psi) TORSION ANGLES: A COMPARATIVE ANALYSIS

A regular secondary structure is described by a well defined set of values for the backbone dihedral angles (phi,psi and omega) in a polypeptide chain. However in real protein structures small local variations give rise to distortions from the ideal structures, which can lead to considerable variation in higher order organization. Protein structure analysis and accurate assignment of various structural elements, especially their terminii, are important first step in protein structure prediction and design. Various algorithms are available for assigning secondary structure elements in proteins but some lacunae still exist. In this study, results of a recently developed in-house program ASSP have been compared with those from STRIDE, in identification of alpha-helical regions in both globular and membrane proteins. It is found that, while a combination of hydrogen bond patterns and backbone torsional angles (phi-psi) are generally used to define secondary structure elements, the geometry of the C-alpha atom trace by itself is sufficient to define the parameters of helical structures in proteins. It is also possible to differentiate the various helical structures by their C-alpha trace and identify the deviations occurring both at mid-positions as well as at the terminii of alpha-helices, which often lead to occurrence of 3(10) and pi-helical fragments in both globular and membrane proteins.

PROTEIN DISULFIDE ANALYSIS AND DESIGN

The significant contribution of naturally occurring disulfide bonds to protein stability has encouraged development of methods to engineer non-native disulfides in proteins. These have yielded mixed results. We summarize applications of the program MODIP for disulfide engineering. The program predicts sites in proteins where disulfides can be stably introduced. The program has also been used as an aid in conformational analysis of naturally occurring disulfides in a-helices, antiparallel and parallel beta-strands. Disulfides in a-helices occur only at N-termini, where the first cysteine residue is the N-cap residue of the helix. The disulfide occurs as a CXXC motif and can possess redox activity. In antiparallel beta-strands, disulfides occur exclusively at non-hydrogen bonded (NHB) registered pairs of antiparallel beta-sheets with only 1 known natural example occurring at a hydrogen bonded (HB) registered pair. Conformational analysis suggests that disulfides between HB residue pairs are under torsional strain. A similar analysis to characterize disulfides in parallel beta-strands was carried out. We observed that only 9 instances of cross-strand disulfides exist in a non-redundant dataset. Stereochemical analysis shows that while tbe chi(square) angles are similar to those of other disulfides, the chi(1) and chi(2) angles show more variation and that one of tbe strands is generally an edge strand.

Parallel Flow-Sensitive Pointer Analysis by Graph-Rewriting

Precise pointer analysis is a problem of interest to both the compiler and the program verification community. Flow-sensitivity is an important dimension of pointer analysis that affects the precision of the final result computed. Scaling flow-sensitive pointer analysis to millions of lines of code is a major challenge. Recently, staged flow-sensitive pointer analysis has been proposed, which exploits a sparse representation of program code created by staged analysis. In this paper we formulate the staged flow-sensitive pointer analysis as a graph-rewriting problem. Graph-rewriting has already been used for flow-insensitive analysis. However, formulating flow-sensitive pointer analysis as a graph-rewriting problem adds additional challenges due to the nature of flow-sensitivity. We implement our parallel algorithm using Intel Threading Building Blocks and demonstrate considerable scaling (upto 2.6x) for 8 threads on a set of 10 benchmarks. Compared to the sequential implementation of staged flow-sensitive analysis, a single threaded execution of our implementation performs better in 8 of the benchmarks.

MolBridge: a program for identifying nonbonded interactions in small molecules and biomolecular structures

Identification and analysis of nonbonded interactions within a molecule and with the surrounding molecules are an essential part of structural studies, given the importance of these interactions in defining the structure and function of any supramolecular entity. MolBridge is an easy to use algorithm based purely on geometric criteria that can identify all possible nonbonded interactions, such as hydrogen bond, halogen bond, cation-pi, pi-pi and van der Waals, in small molecules as well as biomolecules. The user can either upload three-dimensional coordinate files or enter the molecular ID corresponding to the relevant database. The program is available in a standalone form and as an interactive web server with Jmol and JME incorporated into it. The program is freely downloadable and the web server version is also available at http://nucleix.mbu.iisc.ernet.in/molbridge/index.php.