CiteULike: Author Srinivasan

Genome sequencing in microfabricated high-density picolitre reactors

Marcel Margulies — 2005-07-31T21:14:04-00:00

Nature (31 July 2005)

RB loss promotes aberrant ploidy by deregulating levels and activity of DNA replication factors.

SV Srinivasan — 2008-07-21T19:54:52-00:00

The Journal of biological chemistry, Vol. 282, No. 33. (17 August 2007), pp. 23867-23877.

The retinoblastoma tumor suppressor (RB) is functionally inactivated in many human cancers. Classically, RB functions to repress E2F-mediated transcription and inhibit cell cycle progression. Consequently, RB ablation leads to loss of cell cycle control and aberrant expression of E2F target genes. Emerging evidence indicates a role for RB in maintenance of genomic stability. Here, mouse adult fibroblasts were utilized to demonstrate that aberrant DNA content in RB-deficient cells occurs concomitantly with an increase in levels and chromatin association of DNA replication factors. Furthermore, following exposure to nocodazole, RB-proficient cells arrest with 4 n DNA content, whereas RB-deficient cells bypass the mitotic block, continue DNA synthesis, and accumulate cells with higher ploidy and micronuclei. Under this condition, RB-deficient cells also retain high levels of tethered replication factors, MCM7 and PCNA, indicating that DNA replication occurs in these cells under nonpermissive conditions. Exogenous expression of replication factors Cdc6 or Cdt1 in RB-proficient cells does not recapitulate the RB-deficient cell phenotype. However, ectopic E2F expression in RB-proficient cells elevated ploidy and bypassed the response to nocodazole-induced cessation of DNA replication in a manner analogous to RB loss. Collectively, these results demonstrate that deregulated S phase control is a key mechanism by which RB-deficient cells acquire elevated ploidy.

The complete genome of an individual by massively parallel DNA sequencing

David Wheeler — 2008-04-16T19:24:49-00:00

Nature, Vol. 452, No. 7189. (17 April 2008), pp. 872-876.

Protein structure mining using a structural alphabet

M Tyagi — 2008-07-15T09:04:47-00:00

Proteins: Structure, Function, and Bioinformatics, Vol. 71, No. 2. (2008), pp. 920-937.

We present a comprehensive evaluation of a new structure mining method called PB-ALIGN. It is based on the encoding of protein structure as 1D sequence of a combination of 16 short structural motifs or protein blocks (PBs). PBs are short motifs capable of representing most of the local structural features of a protein backbone. Using derived PB substitution matrix and simple dynamic programming algorithm, PB sequences are aligned the same way amino acid sequences to yield structure alignment. PBs are short motifs capable of representing most of the local structural features of a protein backbone. Alignment of these local features as sequence of symbols enables fast detection of structural similarities between two proteins. Ability of the method to characterize and align regions beyond regular secondary structures, for example, N and C caps of helix and loops connecting regular structures, puts it a step ahead of existing methods, which strongly rely on secondary structure elements. PB-ALIGN achieved efficiency of 85% in extracting true fold from a large database of 7259 SCOP domains and was successful in 82% cases to identify true super-family members. On comparison to 13 existing structure comparison/mining methods, PB-ALIGN emerged as the best on general ability test dataset and was at par with methods like YAKUSA and CE on nontrivial test dataset. Furthermore, the proposed method performed well when compared to flexible structure alignment method like FATCAT and outperforms in processing speed (less than 45 s per database scan). This work also establishes a reliable cut-off value for the demarcation of similar folds. It finally shows that global alignment scores of unrelated structures using PBs follow an extreme value distribution. PB-ALIGN is freely available on web server called Protein Block Expert (PBE) at . Proteins 2008. © 2007 Wiley-Liss, Inc.

Modulation of nucleic acid structure by ligand binding: induction of a DNA.RNA.DNA hybrid triplex by DAPI intercalation.

Z Xu — 2008-07-15T00:42:40-00:00

Bioorganic & medicinal chemistry, Vol. 5, No. 6. (June 1997), pp. 1137-1147.

The aromatic diamidine, DAPI (4',6-diamidino-2-phenylindole), is used as an important biological and cytological tool since it forms highly fluorescent complexes with nucleic acid duplexes via minor groove-directed/intercalative modes of interaction. In this study, we find that DAPI binding can induce the formation of an RNA-DNA hybrid triplex that would not otherwise form. More specifically, through application of a broad range of spectroscopic, viscometric, and molecular modeling techniques, we demonstrate that DAPI intercalation induces the formation of the poly(dT).poly(rA).poly(dT) hybrid triple helix, a structure which does not form in the absence of the ligand. Using UV mixing studies, we demonstrate that, in the presence of DAPI, the poly(rA).poly(dT) duplex and the poly(dT) single strand form a 1:1 complex (a triplex) that does not form in the absence of DAPI. Through temperature-dependent absorbance measurements, we show that the poly(dT).poly(rA).poly(dT) triplex melts via two distinct transitions: initial conversion of the triplex to the duplex state, with the DAPI remaining bound, followed by denaturation of the duplex-DAPI complex to its component single strands and free DAPI. Using optical melting profiles, we show that DAPI binding enhances the thermal stability of the poly(dT).poly(rA).poly(dT) triplex, an observation consistent with the preferential binding of the ligand to the triplex versus the duplex and single-stranded states. Our differential scanning calorimetric measurements reveal melting of the DAPI-saturated poly(dT).poly(rA).poly(dT) triplex to be associated with a lower enthalpy but greater cooperativity than melting of the corresponding DAPI-saturated poly(rA).poly(dT) duplex. Our flow linear dichroism and viscometric data are consistent with an intercalative mode of binding when DAPI interacts with both the poly(dT).poly(rA).poly(dT) triplex and the poly(rA).poly(dT) duplex. Finally, computer modeling studies suggest that a combination of both stacking and electrostatic interactions between the intercalated ligand and the host nucleic acid play important roles in the DAPI-induced stabilization of the poly(dT).poly(rA).poly(dT) triplex. In the aggregate, our results demonstrate that ligand binding can be used to induce the formation of triplex structures that do not form in the absence of the ligand. This triplex-inducing capacity has potentially important implications in the design of novel antisense, antigene, antiviral, and diagnostic strategies.

Fusion transcripts and transcribed retrotransposed loci discovered through comprehensive transcriptome analysis using Paired-End diTags (PETs).

Y Ruan — 2007-06-16T07:38:42-00:00

Genome Res, Vol. 17, No. 6. (June 2007), pp. 828-838.

Identification of unconventional functional features such as fusion transcripts is a challenging task in the effort to annotate all functional DNA elements in the human genome. Paired-End diTag (PET) analysis possesses a unique capability to accurately and efficiently characterize the two ends of DNA fragments, which may have either normal or unusual compositions. This unique nature of PET analysis makes it an ideal tool for uncovering unconventional features residing in the human genome. Using the PET approach for comprehensive transcriptome analysis, we were able to identify fusion transcripts derived from genome rearrangements and actively expressed retrotransposed pseudogenes, which would be difficult to capture by other means. Here, we demonstrate this unique capability through the analysis of 865,000 individual transcripts in two types of cancer cells. In addition to the characterization of a large number of differentially expressed alternative 5' and 3' transcript variants and novel transcriptional units, we identified 70 fusion transcript candidates in this study. One was validated as the product of a fusion gene between BCAS4 and BCAS3 resulting from an amplification followed by a translocation event between the two loci, chr20q13 and chr17q23. Through an examination of PETs that mapped to multiple genomic locations, we identified 4055 retrotransposed loci in the human genome, of which at least three were found to be transcriptionally active. The PET mapping strategy presented here promises to be a useful tool in annotating the human genome, especially aberrations in human cancer genomes.

Ilp: a short look back and a longer look forward

David Page — 2008-07-11T00:26:58-00:00

J. Mach. Learn. Res., Vol. 4 (2003), pp. 415-430.

A retrospective review of enteroclysis in patients with obscure gastrointestinal bleeding and chronic abdominal pain of undetermined etiology.

A Malik — 2008-07-08T23:19:03-00:00

Digestive diseases and sciences, Vol. 50, No. 4. (April 2005), pp. 649-655.

Our purpose was to determine the diagnostic utility of enteroclysis in the evaluation of obscure gastrointestinal bleeding and abdominal pain of unknown etiology. This is a retrospective review of 97 consecutive patients (mean age, 54.1+/-17.5 [SD] years; 49 male and 48 female) who underwent enteroclysis at Temple University Hospital from January 1994 to October 2001 for the evaluation of obscure GI bleeding or chronic abdominal pain of undetermined etiology. Prior to enteroclysis all patients had an EGD and colonoscopy, which were nondiagnostic for their symptoms. Sixty-three patients (64.9%) had enteroscopy performed prior to enteroclysis that was also negative. Enteroclysis results were defined as positive based on anatomical or functional abnormalities. Analysis of the data included the percentage yield of positive exams, the percentage of positive results per symptom category, and the percentage of patients with a change in clinical management based on positive enteroclysis results. Ninety-seven patients underwent enteroclysis. The indications for enteroclysis were obscure GI bleeding in 67 patients (69.1%) and chronic abdominal pain in 30 patients (30.9%). The number of positive exams was 19 (19.6%). Fourteen of the 67 patients with the indication of GI bleeding had a positive exam (21%), while 5 of the 30 patients with chronic abdominal pain had a positive result (16.7%). There was a change in clinical management due to the enteroclysis results in 10 patients: 7 patients with GI bleeding (10%) and 3 patients with chronic abdominal pain (10%). Positive enteroclysis findings included adhesions (7), filling defects and masses (5), strictures (2), small bowel diverticulosis (1), mucosal abnormalities (3), and a motility disorder (1). The overall positive yield for enteroclysis was 19.6%, with a yield of 16.7% for chronic abdominal pain and 21% for gastrointestinal bleeding. Enteroclysis results changed the clinical management in approximately 10% of the patients.

Fast distributed algorithms for (weakly) connected dominating sets and linear-size skeletons

Devdatt Dubhashi — 2008-07-08T21:07:16-00:00

J. Comput. Syst. Sci., Vol. 71, No. 4. (November 2005), pp. 467-479.

Honeybee Odometry: Performance in Varying Natural Terrain

Juergen Tautz — 2008-07-07T00:04:51-00:00

PLoS Biology, Vol. 2, No. 7. (1 July 2004), e211.

Recent studies have shown that honeybees flying through short, narrow tunnels with visually textured walls perform waggle dances that indicate a much greater flight distance than that actually flown. These studies suggest that the bee's “odometer” is driven by the optic flow (image motion) that is experienced during flight. One might therefore expect that, when bees fly to a food source through a varying outdoor landscape, their waggle dances would depend upon the nature of the terrain experienced en route. We trained honeybees to visit feeders positioned along two routes, each 580 m long. One route was exclusively over land. The other was initially over land, then over water and, finally, again over land. Flight over water resulted in a significantly flatter slope of the waggle-duration versus distance regression, compared to flight over land. The mean visual contrast of the scenes was significantly greater over land than over water. The results reveal that, in outdoor flight, the honeybee's odometer does not run at a constant rate; rather, the rate depends upon the properties of the terrain. The bee's perception of distance flown is therefore not absolute, but scene-dependent. These findings raise important and interesting questions about how these animals navigate reliably.

Japanese and U.S. Firms as Foreign Investors: Do They March to the Same Tune?

Ashoka Mody — 2007-02-12T19:54:58-00:00

The Canadian Journal of Economics / Revue canadienne d'Economique, Vol. 31, No. 4. (1998), pp. 778-799.

During the 1980s, U.S. and Japanese multinationals were attracted by some similar country characteristics: low wage inflation, low country risk, good infrastructure, and an educated work force. Both groups of investors displayed a persistence, being strongly attracted to locations with significant past investment. Japanese firms started the decade as somewhat more fluid, but as their investment levels surged, they became much more persistent. Overall, U.S. firms were more influenced by domestic market conditions and moved contrary to changes in host country trade intensity. Japanese investment had a somewhat greater affinity for trade, reflecting their long-standing interest in East Asia. Some limited evidence suggests that factors driving the two groups of investors converged in the second half of the 1980s. JEL Classification: J441, J442

Supporting time-constrained SQL queries in oracle

Ying Hu — 2008-07-04T12:34:48-00:00

(2007), pp. 1207-1218.

Sexual reproduction selects for robustness and negative epistasis in artificial gene networks

Ricardo Azevedo — 2006-03-01T19:55:41-00:00

Nature, Vol. 440, No. 7080. (2006), pp. 87-90.

The mutational deterministic hypothesis for the origin and maintenance of sexual reproduction posits that sex enhances the ability of natural selection to purge deleterious mutations after recombination brings them together into single genomes1. This explanation requires negative epistasis, a type of genetic interaction where mutations are more harmful in combination than expected from their separate effects. The conceptual appeal of the mutational deterministic hypothesis has been offset by our inability to identify the mechanistic and evolutionary bases of negative epistasis. Here we show that negative epistasis can evolve as a consequence of sexual reproduction itself. Using an artificial gene network model2, 3, we find that recombination between gene networks imposes selection for genetic robustness, and that negative epistasis evolves as a by-product of this selection. Our results suggest that sexual reproduction selects for conditions that favour its own maintenance, a case of evolution forging its own path.

Interaction preferences across protein-protein interfaces of obligatory and non-obligatory components are different.

S De — 2006-05-11T14:25:28-00:00

BMC Struct Biol, Vol. 5 (16 August 2005)

BACKGROUND: A polypeptide chain of a protein-protein complex is said to be obligatory if it is bound to another chain throughout its functional lifetime. Such a chain might not adopt the native fold in the unbound form. A non-obligatory polypeptide chain associates with another chain and dissociates upon molecular stimulus. Although conformational changes at the interaction interface are expected, the overall 3-D structure of the non-obligatory chain is unaltered. The present study focuses on protein-protein complexes to understand further the differences between obligatory and non-obligatory interfaces. RESULTS: A non-obligatory chain in a complex of known 3-D structure is recognized by its stable existence with same fold in the bound and unbound forms. On the contrary, an obligatory chain is detected by its existence only in the bound form with no evidence for the native-like fold of the chain in the unbound form. Various interfacial properties of a large number of complexes of known 3-D structures thus classified are comparatively analyzed with an aim to identify structural descriptors that distinguish these two types of interfaces. We report that the interaction patterns across the interfaces of obligatory and non-obligatory components are different and contacts made by obligatory chains are predominantly non-polar. The obligatory chains have a higher number of contacts per interface (20 +/- 14 contacts per interface) than non-obligatory chains (13 +/- 6 contacts per interface). The involvement of main chain atoms is higher in the case of obligatory chains (16.9 %) compared to non-obligatory chains (11.2 %). The beta-sheet formation across the subunits is observed only among obligatory protein chains in the dataset. Apart from these, other features like residue preferences and interface area produce marginal differences and they may be considered collectively while distinguishing the two types of interfaces. CONCLUSION: These results can be useful in distinguishing the two types of interfaces observed in structures determined in large-scale in the structural genomics initiatives, especially for those multi-component protein assemblies for which the biochemical characterization is incomplete.

Experimental demonstration of evanescent coupling from optical fibre tapers to photonic crystal waveguides

PE Barclay — 2008-07-03T09:05:38-00:00

Electronics Letters, Vol. 39, No. 11. (2003), pp. 842-844.

Experimental results demonstrating nearly complete mode-selective evanescent coupling to a photonic crystal waveguide from an optical fibre taper are presented. Codirectional coupling with 98% maximum power transfer to a photonic crystal waveguide of length 65 /spl mu/m and with a coupling bandwidth of 20 nm is realised.

Nonlinear response of silicon photonic crystal microresonators excited via an integrated waveguide and fiber taper

Paul Barclay — 2008-07-03T09:02:31-00:00

Opt. Express, Vol. 13, No. 3. (7 February 2005), pp. 801-820.

A technique is demonstrated which efficiently transfers light between a tapered standard single-mode optical fiber and a high-Q, ultra-small mode volume, silicon photonic crystal resonant cavity. Cavity mode quality factors of 4.7×10 4 are measured, and a total fiber-to-cavity coupling efficiency of 44% is demonstrated. Using this efficient cavity input and output channel, the steady-state nonlinear absorption and dispersion of the photonic crystal cavity is studied. Optical bistability is observed for fiber input powers as low as 250 µW, corresponding to a dropped power of 100 µW and 3 fJ of stored cavity energy. A high-density effective free-carrier lifetime for these silicon photonic crystal resonators of ~ 0.5 ns is also estimated from power dependent loss and dispersion measurements.

Design of photonic crystal waveguides for evanescent coupling to optical fiber tapers and integration with high-Q cavities

Paul Barclay — 2008-07-03T08:55:10-00:00

J. Opt. Soc. Am. B, Vol. 20, No. 11. (1 November 2003), pp. 2274-2284.

We describe a novel scheme based on evanescent guided-wave coupling for optically interfacing between conventional fiber-optic and planar photonic crystal devices such as waveguides and resonant cavities. By considering the band structure of bulk photonic crystal slabs, we analyze the k space properties of a linear defect waveguide and establish a set of design rules to ensure efficient evanescent coupling with optical fiber tapers. These rules are used to design a waveguide in a square-lattice photonic crystal. The coupling efficiency is calculated with a coupled-mode theory incorporating the finite-difference time-domain-calculated uncoupled modes of the fiber taper and photonic crystal waveguide. On the basis of this coupled-mode theory, 95% power transfer from the fiber taper to the photonic crystal waveguide is possible over a coupling length of 80 lattice periods and with a bandwidth of 1.5% of the center wavelength. The integration of this waveguide with a photonic crystal defect resonant cavity is also presented, thus showing the usefulness of the combined fiber taper and photonic crystal waveguide system for efficient, optical fiber-based probing of optical elements based on planar photonic crystal technologies.

Engineering the melanocortin-4 receptor to control constitutive and ligand-mediated G(S) signaling in vivo.

S Srinivasan — 2008-07-02T23:32:40-00:00

PLoS ONE, Vol. 2, No. 7. (2007)

The molecular and functional diversity of G protein-coupled receptors is essential to many physiological processes. However, this diversity presents a significant challenge to understanding the G protein-mediated signaling events that underlie a specific physiological response. To increase our understanding of these processes, we sought to gain control of the timing and specificity of G(s) signaling in vivo. We used naturally occurring human mutations to develop two G(s)-coupled engineered receptors that respond solely to a synthetic ligand (RASSLs). Our G(s)-coupled RASSLs are based on the melanocortin-4 receptor, a centrally expressed receptor that plays an important role in the regulation of body weight. These RASSLs are not activated by the endogenous hormone alpha-melanocyte-stimulating hormone but respond potently to a selective synthetic ligand, tetrahydroisoquinoline. The RASSL variants reported here differ in their intrinsic basal activities, allowing the separation of the effects of basal signaling from ligand-mediated activation of the G(s) pathway in vivo. These RASSLs can be used to activate G(s) signaling in any tissue, but would be particularly useful for analyzing downstream events that mediate body weight regulation in mice. Our study also demonstrates the use of human genetic variation for protein engineering.

Protein intermediate trapped by the simultaneous crystallization process. Crystal structure of an iron-saturated intermediate in the Fe3+ binding pathway of camel lactoferrin at 2.7 a resolution.

JA Khan — 2008-07-02T11:56:53-00:00

The Journal of biological chemistry, Vol. 276, No. 39. (28 September 2001), pp. 36817-36823.

This is the first protein intermediate obtained in the crystalline state by the simultaneous process of Fe(3+) binding and crystal nucleation and is also the first structure of an intermediate of lactoferrin in the Fe(3+) binding pathway. Lactoferrin is an iron-binding 80-kDa glycoprotein. It binds Fe(3+) very tightly in a closed interdomain cleft in both lobes. The iron-free structure of lactoferrin, on the other hand, adopts an open conformation with domains moving widely apart. These studies imply that initial Fe(3+) binding must be in the open form. The protein intermediate was crystallized by the microdialysis method. The protein solution, with a concentration of 100 mg/ml in 10 mm Tris-HCl, pH 8.0, was loaded in a capillary and dialyzed against the same buffer containing 26% (v/v) ethanol placed in a reservoir. FeCl(3) and CO(3)(2-) in excess molar ratios to that of protein in its solution were added to the reservoir buffer. The crystals appeared after some hours and grew to the optimum size within 36 h. The structure was determined by molecular replacement method and refined to final R- and R-free factors of 0.187 and 0.255, respectively. The present structure showed that the protein molecule adopts an open conformation similar to that of camel apolactoferrin. The electron density map clearly indicated the presence of two iron atoms, one in each lobe with 4-fold coordinations: two by the protein ligands of Tyr-92(433) OH and Tyr-192(526) OH and two other coordination sites occupied by oxygen atoms of bidentate CO(3)(2-) ions leading to a tetrahedral intermediate. The CO(3)(2-) anion is stabilized through hydrogen bonds with the synergistic anion-binding site Arg-121(463) and with Ser-122 Ogamma in the N-lobe and Thr-464 Ogamma in C-lobe. The third oxygen atom of CO(3)(2-) interacts with a water molecule in both lobes.

Link Contexts in Classifier-Guided Topical Crawlers

Gautam Pant — 2006-01-20T11:51:45-00:00

IEEE Transactions on Knowledge and Data Engineering, Vol. 18, No. 1. (January 2006), pp. 107-122.

PN Code Tracking Using Noncommensurate Sampling

KJ Quirk — 2008-06-27T11:08:15-00:00

Communications, IEEE Transactions on, Vol. 54, No. 7. (2006), pp. 1349-1349.

The use of a noninteger symbol to sample time ratio, noncommensurate sampling, in pseudonoise (PN) code-tracking loops is investigated. A noncoherent PN code-tracking loop using noncommensurate sampling and single-bit quantization is presented. An analysis method is developed to characterize the system and determine the steady-state error variance of the timing estimate. The performance of an equivalent analog code-tracking loop is derived and compared with the digital loop to investigate the degradation incurred through sampling and quantization.

Current progress in network research: toward reference networks for key model organisms.

Balaji S Srinivasan — 2007-09-04T08:40:39-00:00

Brief Bioinform (29 August 2007)

The collection of multiple genome-scale datasets is now routine, and the frontier of research in systems biology has shifted accordingly. Rather than clustering a single dataset to produce a static map of functional modules, the focus today is on data integration, network alignment, interactive visualization and ontological markup. Because of the intrinsic noisiness of high-throughput measurements, statistical methods have been central to this effort. In this review, we briefly survey available datasets in functional genomics, review methods for data integration and network alignment, and describe recent work on using network models to guide experimental validation. We explain how the integration and validation steps spring from a Bayesian description of network uncertainty, and conclude by describing an important near-term milestone for systems biology: the construction of a set of rich reference networks for key model organisms.

Pipeline spectroscopy

TR Puzak — 2008-06-25T18:15:24-00:00

(2007), pp. 16-16.

Comparative kinomics of Plasmodium organisms: unity in diversity.

K Anamika — 2007-12-02T07:25:13-00:00

Protein Pept Lett, Vol. 14, No. 6. (2007), pp. 509-517.

Phosphorylation by protein kinases is a very common and crucial process in many signal transduction pathways in eukaryotes. This review describes comparative protein kinase analysis of two apicomplexa Plasmodium falciparum (3D7 strain) and Plasmodium yoelii yoelii (17XNL strain) which are causative agents of malaria in human and African rat respectively. Sensitive bioinformatics techniques enable identification of 82 and 60 putative protein kinases in P. falciparum and P. yoelii yoelii respectively and these sequences could be classified into known subfamilies of protein kinases. The most populated kinase subfamilies in both the plasmodium species correspond to CAMK and CMGC groups. Analysis of domain architectures enables detection of uncommon domain organization in kinases of both the organisms such as kinase domain tethered to EF hands as well as PH domain. Components of MAPK signaling pathway is not well conserved in plasmodium organisms. Such observations suggest that plasmodium protein kinases are highly divergent from other eukaryotes. A transmembrane kinase with 6 membrane spanning segments in P. falciparum seems to have no orthologue in P. yoelii yoelii. 19 P. falciparum kinases have been found to cluster separately from P. yoelii yoelii kinases and hence these kinases are unique to P. falciparum genome. Only 28 orthologous pairs of kinases seem to be present between these two plasmodium organisms. Comparative kinome analysis of two plasmodium species has thus provided clues to the function of many protein kinases based upon their classification and domain organization and also implicate marked differences even between two plasmodium organisms.

Functional genome annotation through phylogenomic mapping

Balaji Srinivasan — 2005-06-07T08:20:31-00:00

Nature Biotechnology, Vol. 23, No. 6. (06 June 2005), pp. 691-698.

Lexical methods for managing variation in biomedical terminologies.

AT McCray — 2007-08-06T13:40:12-00:00

Proc Annu Symp Comput Appl Med Care (1994), pp. 235-239.

Access to biomedical terminologies is hampered by the high degree of variability inherent in natural language terms and in the terminologies themselves. The lexicon, lexical programs, databases, and indexes included with the 1994 release of the UMLS Knowledge Sources are designed to help users manage this variability. We describe these resources and illustrate their flexibility and usefulness in providing enhanced access to data in the UMLS Metathesaurus.

A comprehensive analysis of protein-protein interactions in Saccharomyces cerevisiae

Peter Uetz — 2005-06-13T22:55:54-00:00

Nature, Vol. 403, No. 6770. (10 February 2000), pp. 623-627.

Identification of wave-like spatial structure in the SSVEP: comparison of simultaneous EEG and MEG.

SG Thorpe — 2008-06-10T16:09:56-00:00

Statistics in medicine, Vol. 26, No. 21. (20 September 2007), pp. 3911-3926.

Steady-state visual-evoked potentials/fields (SSVEPs/SSVEFs) are used in cognitive and clinical electroencephalogram (EEG) and magnetoencephalogram (MEG) studies because of their excellent signal-to-noise ratios and relative immunity to artifact. Steady-state paradigms are also used to characterize preferred frequencies of dynamic neocortical processes. In this study, SSVEPs and SSVEFs were simultaneously recorded while subjects viewed checkerboard patterns alternating (black to white, white to black) with fixed driving frequency between 2 and 20 Hz. Distinct peaks in SSVEP/SSVEF power were observed in the theta (4-8 Hz) and upper alpha (10-14 Hz) bands. A distinct peak in SSVEP power was also observed in the beta band (between 15 and 20 Hz) which had no counterpart in the MEG. One-dimensional spatial spectra indicate that distinct large-scale source distributions contribute to SSVEP power in the upper alpha band in the form of long wavelength (lambda>20 cm) traveling waves propagating from occipital to prefrontal electrodes. In the beta band, spatial spectra and SSVEF indicate that long-wavelength source distributions over posterior and anterior regions form standing wave patterns. These results suggest that simple models of SSVEP based on a single dipole source in the occipital lobe are inadequate to explain the dynamic spatial patterns of SSVEP magnitude and phase. Theoretical models of SSVEP should include multiple local and distributed sources and exhibit both traveling and standing wave dynamics.

Smoothed particle hydrodynamics techniques for the solution of kinetic theory problems Part 1: Method

CV Chaubal — 2008-06-06T14:38:33-00:00

Journal of Non-Newtonian Fluid Mechanics, Vol. 70, No. 1-2. (May 1997), pp. 125-154.

The smoothed particle hydrodynamics (SPH) technique has been applied to a problem in kinetic theory, namely, the dynamics of liquid crystalline polymers (LCPs). It is a Lagrangian solution method developed for fluid flow calculations; its adaption to kinetic theory is outlined. The Lagrangian formulation of the Doi theory for LCPs is first described, and the problem is presented in the general framework of nonparametric density estimation. The implementation of the SPH technique in this specific problem is given, highlighting particular aspects of our implementation of SPH, including the form of the kernel function and use of an adaptive kernel. We then present results which demonstrate convergence and other details of the solution method, and also make comparisons with other solution techniques and discuss other potential applications.

Principal components analysis based methodology to identify differentially expressed genes in time-course microarray data

Sudhakar Jonnalagadda — 2008-06-06T07:33:07-00:00

BMC Bioinformatics, Vol. 9 (06 June 2008), 267.

Cooperation in wireless ad hoc networks

V Srinivasan — 2008-05-30T19:07:36-00:00

(2003)

In wireless ad hoc networks, nodes communicate with far off destinations using intermediate nodes as relays. Since wireless nodes are energy constrained, it may not be in the best interest of a node to always accept relay requests. On the other hand, if all nodes decide not to expend energy in relaying, then network throughput will drop dramatically. Both these extreme scenarios (complete cooperation and complete noncooperation) are inimical to the interests of a user. In this paper we address...

Integrated Protein Interaction Networks for 11 Microbes

Balaji Srinivasan — 2007-03-03T22:10:20-00:00

: Research in Computational Molecular Biology (2006), pp. 1-14.

Pricing and rebate policies in the two-echelon supply chain with asymmetric information under price-dependent, stochastic demand

FJ Arcelus — 2008-05-23T00:02:14-00:00

International Journal of Production Economics, Vol. 113, No. 2. (June 2008), pp. 598-618.

This paper analyzes the manufacturers' strategy of optimizing the direct rebate to the final customer and the wholesale price to a profit-maximizing retailer with a price-dependent stochastic demand. The manufacturer possesses full information about the cost and the functional relationship among demand, price and rebate, but may or may not know about the nature of the underlying demand uncertainty faced by the retailer. The conditions under which a retailer benefits from passing on such information are identified. The main features of the model are illustrated analytically and numerically, using linear or iso-elastic demand functions, with additive or multiplicative error structures. Several important implications have been derived, especially those dealing with price and rebate pass-throughs and with the cost to the manufacturer of asymmetric information.

P/sup 5/ : a protocol for scalable anonymous communication

R Sherwood — 2008-05-22T19:48:29-00:00

Security and Privacy, 2002. Proceedings. 2002 IEEE Symposium on (2002), pp. 58-70.

We present a protocol for anonymous communication over the Internet. Our protocol, called P/sup 5/ (peer-to-peer personal privacy protocol) provides sender-, receiver-, and sender-receiver anonymity. P/sup 5/ is designed to be implemented over current Internet protocols, and does not require any special infrastructure support. A novel feature of P/sup 5/ is that it allows individual participants to trade-off degree of anonymity for communication efficiency, and hence can be used to scalably implement large anonymous groups. We present a description of P/sup 5/, an analysis of its anonymity and communication efficiency, and evaluate its performance using detailed packet-level simulations.

Renin angiotensin system blockade and cardiovascular outcomes in patients with chronic kidney disease and proteinuria: a meta-analysis.

S Balamuthusamy — 2008-05-22T08:49:20-00:00

American heart journal, Vol. 155, No. 5. (May 2008), pp. 791-805.

OBJECTIVE: The role of renin angiotensin system (RAS) blockade in controlling hypertension and the positive impact on cardiovascular (CV) outcomes is well known. However, the role of RAS blockade in improving CV outcomes in patients with chronic kidney disease (CKD) is still unclear. METHODS: Randomized controlled trials that analyzed CV outcomes in patients with CKD/proteinuria treated with RAS blockade (angiotensin-converting enzyme inhibitors/angiotensin receptor blockers) were included in our study. The relative risk across all study groups was computed using Mantel-Hanszel random effects model. Results were calculated with 95% CI and was considered statistically significant if 2-sided alpha error was <.05. Renin angiotensin system blockade-based therapy was compared with placebo and control (beta-blocker, calcium-channel blockers and other antihypertensive-based therapy) therapy in the study. RESULTS: Twenty-five trials (N = 45758) were used for analysis. Renin angiotensin system blockade decreased the risk for heart failure in patients with diabetic nephropathy when compared with placebo 0.78 (95% CI 0.66-0.92, P = .003) and control therapy (0.63, 95% CI 0.47-0.86, P = .003). The risk for CV outcomes was decreased with RAS blockade (0.56, 95% CI 0.47-0.67, P < .001) in nondiabetic nephropathy patients with CKD when compared with control therapy. There was also a significant reduction of CV outcomes (0.84, 95% CI 0.78-0.91, P < .0001), myocardial infarction (0.78, 95% CI 0.65-0.97, P = .03), and heart failure (0.74, 95% CI 0.58-0.95, P = .02) when we pooled all the patients with CKD and compared RAS blockade to placebo. CONCLUSIONS: A pooled analysis of all causes of CKD revealed a reduction in the risk for myocardial infarction, heart failure, and total CV outcomes when RAS blockade was compared with placebo. RAS blockade decreases the risk for CV outcomes and heart failure when compared with control therapy in patients with proteinuria. There were also benefits with RAS blockade in reducing the risk of CV outcomes and heart failure in patients with diabetic nephropathy when compared with placebo.

Experimental demonstration of a high quality factor photonic crystal microcavity

Kartik Srinivasan — 2007-03-01T21:05:19-00:00

Applied Physics Letters, Vol. 83, No. 10. (2003), pp. 1915-1917.

Subthreshold measurements of a photonic crystal (PC) microcavity laser operating at 1.3 µm show a linewidth of 0.10 nm, corresponding to a quality factor (Q)~1.3×104. The PC microcavity mode is a donor-type mode in a graded square lattice of air holes, with a theoretical Q~105 and mode volume Veff~0.25 cubic half-wavelengths in air. Devices are fabricated in an InAsP/InGaAsP multi-quantum-well membrane and are optically pumped at 830 nm. External peak pump power laser thresholds as low as 100 µW are also observed. ©2003 American Institute of Physics.

Bringing Semantics to Web Services: The OWL-S Approach

David Martin — 2008-05-20T22:24:25-00:00

Semantic Web Services and Web Process Composition (2005), pp. 26-42.

Service interface description languages such as WSDL, and related standards, are evolving rapidly to provide a foundation for interoperation between Web services. At the same time, Semantic Web service technologies, such as the Ontology Web Language for Services (OWL-S), are developing the means by which services can be given richer semantic specifications. Richer semantics can enable fuller, more flexible automation of service provision and use, and support the construction of more powerful tools and methodologies. Both sets of technologies can benefit from complementary uses and cross-fertilization of ideas. This paper shows how to use OWL-S in conjunction with Web service standards, and explains and illustrates the value added by the semantics expressed in OWL-S.

Stereochemical modeling of disulfide bridges. Criteria for introduction into proteins by site-directed mutagenesis

R Sowdhamini — 2008-05-19T10:06:27-00:00

Protein Eng., Vol. 3, No. 2. (1 November 1989), pp. 95-103.

A computer modeling procedure for assessing the stereochemical suitability of pairs of residues in proteins as potential sites for introduction of cystine disulfide crosslinks has been developed. Residue pairs with Calpha - Calpha distances of [≤]6.5 A and Cbeta;-Cbeta distances of [≤]4.5 A are chosen for geometrical fixation of S atoms using the program MODIP. The stereochemistry of the modeled disulfides is evaluated using limits for the structural parameters of the various torsion angles and S-S bond length in the disulfide bridge. The ability of the procedure to correctly model disulfides has been checked with examples of cystine peptides of known crystal structures and 103 disulfide bridges from 25 available protein crystal structures determined at [≤]2 A resolution. An analysis of results on three proteins with engineered disulfides, T4 lysozyme, dihydrofolate reductase and subtilisin, is presented. Two positions for the introduction of stereochemically optimal' disulfides are identified in subtilisin. 10.1093/protein/3.2.95

MR imaging methods for assessing fetal brain development.

M Rutherford — 2008-05-15T14:23:06-00:00

Developmental neurobiology, Vol. 68, No. 6. (May 2008), pp. 700-711.

Fetal magnetic resonance imaging provides an ideal tool for investigating growth and development of the brain in vivo. Current imaging methods have been hampered by fetal motion but recent advances in image acquisition can produce high signal to noise, high resolution 3-dimensional datasets suitable for objective quantification by state of the art post acquisition computer programs. Continuing development of imaging techniques will allow a unique insight into the developing brain, more specifically process of cell migration, axonal pathway formation, and cortical maturation. Accurate quantification of these developmental processes in the normal fetus will allow us to identify subtle deviations from normal during the second and third trimester of pregnancy either in the compromised fetus or in infants born prematurely. (c) 2008 Wiley Periodicals, Inc. Develop Neurobiol, 2008.

3-D CENTERLINE EXTRACTION OF AXONS IN MICROSCOPIC STACKS FOR THE STUDY OF MOTOR NEURON BEHAVIOR IN DEVELOPING MUSCLES

R Srinivasan — 2008-05-13T09:29:42-00:00

Biomedical Imaging: From Nano to Macro, 2007. ISBI 2007. 4th IEEE International Symposium on (2007), pp. 93-96.

This paper presents a new algorithm for extracting the centerlines of the axons from 3-D data stacks collected from a laser scanning confocal microscope. Recovery of neuronal structure from such datasets is critical for quantitatively addressing a range of basic biological questions such as the manner in which the branching pattern of motor neurons change during synapse elimination. The presence of artifacts in the cross-sectional images such as blurred boundaries and non-uniform intensities, makes the process of centerline extraction rather challenging. Although many methods exist in practice today, they are either error-prone or involve manual interaction to a large extent, when applied to this particular problem. We propose a robust probabilistic region growing algorithm to extract the centers from the datasets with minimal user interaction

Quasi Monte Carlo-based isotropic distribution of gradient directions for improved reconstruction quality of 3D EPR imaging

Rizwan Ahmad — 2008-05-12T16:58:51-00:00

Journal of Magnetic Resonance, Vol. 184, No. 2. (February 2007), pp. 236-245.

In continuous wave (CW) electron paramagnetic resonance imaging (EPRI), high quality of reconstructed image along with fast and reliable data acquisition is highly desirable for many biological applications. An accurate representation of uniform distribution of projection data is necessary to ensure high reconstruction quality. The current techniques for data acquisition suffer from nonuniformities or local anisotropies in the distribution of projection data and present a poor approximation of a true uniform and isotropic distribution. In this work, we have implemented a technique based on Quasi-Monte Carlo method to acquire projections with more uniform and isotropic distribution of data over a 3D acquisition space. The proposed technique exhibits improvements in the reconstruction quality in terms of both mean-square-error and visual judgment. The effectiveness of the suggested technique is demonstrated using computer simulations and 3D EPRI experiments. The technique is robust and exhibits consistent performance for different object configurations and orientations.

Melatonin, environmental light, and breast cancer

V Srinivasan — 2008-05-10T01:58:41-00:00

Breast Cancer Research and Treatment, Vol. 108, No. 3. (20 April 2008), pp. 339-350.

Abstract Although many factors have been suggested as causes for breast cancer, the increased incidence of the disease seen in women working in night shifts led to the hypothesis that the suppression of melatonin by light or melatonin deficiency plays a major role in cancer development. Studies on the 7,12-dimethylbenz[a]anthracene and N-methyl-N-nitrosourea experimental models of human breast cancer indicate that melatonin is effective in reducing cancer development. In vitro studies in MCF-7 human breast cancer cell line have shown that melatonin exerts its anticarcinogenic actions through a variety of mechanisms, and that it is most effective in estrogen receptor (ER) α-positive breast cancer cells. Melatonin suppresses ER gene, modulates several estrogen dependent regulatory proteins and pro-oncogenes, inhibits cell proliferation, and impairs the metastatic capacity of MCF-7 human breast cancer cells. The anticarcinogenic action on MCF-7 cells has been demonstrated at the physiological concentrations of melatonin attained at night, suggesting thereby that melatonin acts like an endogenous antiestrogen. Melatonin also decreases the formation of estrogens from androgens via aromatase inhibition. Circulating melatonin levels are abnormally low in ER-positive breast cancer patients thereby supporting the melatonin hypothesis for breast cancer in shift working women. It has been postulated that enhanced endogenous melatonin secretion is responsible for the beneficial effects of meditation as a form of psychosocial intervention that helps breast cancer patients.

Effect of nesiritide on renal function in patients admitted for decompensated heart failure.

S Arora — 2008-05-09T10:13:39-00:00

QJM : monthly journal of the Association of Physicians, Vol. 100, No. 11. (November 2007), pp. 699-706.

BACKGROUND: Studies addressing the effect of nesiritide on renal function in patients hospitalized for decompensated heart failure (HF) are limited, with conflicting results. AIM: To study the effect of nesiritide on renal function in patients admitted for acute decompensated HF. METHODS: We retrospectively reviewed charts of patients admitted with decompensated HF, comparing those who received nesiritide along with conventional therapy vs. those who received conventional therapy alone. Serum creatinine levels and body weight were measured on admission, and were compared with levels at day 3 to estimate deterioration in renal function. Worsening renal function (WRF) was defined as a rise in serum creatinine of > or =0.3 mg/dl from baseline, with final creatinine level >1.5 mg/dl. RESULTS: We reviewed 206 charts (116 controls, 90 nesiritide group). WRF developed in 28/90 (31.1%) in the nesiritide group and 37/116 (31.9%) controls (p = 1.0). Mean change in creatinine in the nesiritide group was 0.15 +/- 0.37 mg/dl, compared to 0.17 +/- 0.25 mg/dl in controls (p = 0.75). Using an alternative cut-off increase in serum creatinine of > or =0.5 mg/dl, 16/90 (17.7%) patients in the nesiritide group developed WRF compared to 18/116 (15.5%) controls (p = 0.80). If WRF was defined as elevation in serum creatinine levels by > or =0.3 mg/dl anytime during hospitalization, the incidence of WRF in the nesiritide group remained similar to that of controls (42.2% vs. 41.3%, p = 0.90). On multivariate analysis, nesiritide therapy was not associated with WRF (OR 0.8, 95% CI 0.4-1.6, p = 0.48). DISCUSSION: We failed to detect any significant risk of WRF in patients treated with nesiritide compared to conventional therapy in patients with decompensated HF during index hospitalization. Larger randomized, placebo-controlled trials are required to further elucidate the effect of nesiritide on renal function in these patients.

Crawling the Web

G Pant — 2008-05-09T07:36:22-00:00

(2004)

this document to represent the vocabulary (feature space) that will be used for classification

Energy-Efficient Joint Source-Channel Coding for Optical Wireless Underwater Networks

B Srinivasan — 2008-05-09T02:15:58-00:00

Oceans 2007 (2007), pp. 1-5.

We describe a novel joint source-channel coding scheme for short-range optical wireless links in underwater sensor networks. We present a procedure that maps source symbol sequences to ON-OFF waveforms in the modulation space such that the energy consumption of modulation per source symbol is minimized. We apply this procedure to two settings: the single-dimensional and vector i.i.d. source processes. We show that the energy consumption per source symbol decreases as the length of the modulation waveform increases; however, for a fixed length modulation waveform, this decrease is not monotonic in the length of the source symbol sequence used. We present simulation results for two Gaussian processes that are correlated with each other, and quantitatively demonstrate the effects of the correlation coefficient between the two processes on the minimum energy of modulation that can be achieved per vector source symbol.

A Hybrid Scalable Group Key Management Approach for Large Dynamic Multicast Networks

T Srinivasan — 2008-05-08T15:26:20-00:00

(2006)

On the Use of Lexeme Features for Writer Verification

A Bhardwaj — 2007-12-12T13:51:36-00:00

Document Analysis and Recognition, 2007. ICDAR 2007 Vol. 2. Ninth International Conference on, Vol. 2 (2007), pp. 1088-1092.

Document examiners use a variety of features to analyze a given handwritten document for writer verification. The challenge in the automatic classification of a pair of doc- uments to belong to the same or different writer, are both (i)The task of proper selection and extraction of features from the handwritten document and (ii)The use of a proper model that is capable of utilizing the true discriminatory power of these features for classification. This paper de- scribes the use of content specific skeleton based features for characters and pairs of characters (bigrams) and as- certains their discriminatory power. A triangulation skele- tonisation procedure is first used to obtain the skeleton of the character(s), and features are computed from the skele- ton. Experiments and results are conducted on content spe- cific features extracted for two most frequently occurring bigrams (th, he), and characters (d and f). A neural net- work based on a Bayesian formulation was used to ascer- tain the discriminability power of these features. To com- bine these features with previously existing writer verifica- tion features, an alternative Naive Bayes model is also de- scribed and evaluated. From the results obtained, we con- clude that bigram th has the highest discriminatory power followed by character d, f and bigram he. Also the paper highlights the significant increase in performance of writer verification( 15% more) with the use of Bayesian neural networks as against the Naive Bayes model.

Features for unsupervised document classification

SH Srinivasan — 2008-03-26T21:14:58-00:00

(2002), pp. 1-7.

Lymphoproliferative disease and autoimmunity in mice with increased miR-17-92 expression in lymphocytes

Changchun Xiao — 2008-03-19T16:32:07-00:00

Nature Immunology, Vol. 9, No. 4. (09 March 2008), pp. 405-414.

Airborne traffic surveillance systems: video surveillance of highway traffic

Suman Srinivasan — 2008-04-29T05:15:18-00:00

(2004), pp. 131-135.