Novel melody line identification algorithm for polyphonic MIDI music

The problem of automatic melody line identification in a MIDI file plays an important role towards taking QBH systems to the next level. We present here, a novel algorithm to identify the melody line in a polyphonic MIDI file. A note pruning and track/channel ranking method is used to identify the melody line. We use results from musicology to derive certain simple heuristics for the note pruning stage. This helps in the robustness of the algorithm, by way of discarding "spurious" notes. A ranking based on the melodic information in each track/channel enables us to choose the melody line accurately. Our algorithm makes no assumption about MIDI performer specific parameters, is simple and achieves an accuracy of 97% in identifying the melody line correctly. This algorithm is currently being used by us in a QBH system built in our lab.

Nonlinear structural dynamical system identification using adaptive particle filters

The problem of identifying parameters of nonlinear vibrating systems using spatially incomplete, noisy, time-domain measurements is considered. The problem is formulated within the framework of dynamic state estimation formalisms that employ particle filters. The parameters of the system, which are to be identified, are treated as a set of random variables with finite number of discrete states. The study develops a procedure that combines a bank of self-learning particle filters with a global iteration strategy to estimate the probability distribution of the system parameters to be identified. Individual particle filters are based on the sequential importance sampling filter algorithm that is readily available in the existing literature. The paper develops the requisite recursive formulary for evaluating the evolution of weights associated with system parameter states. The correctness of the formulations developed is demonstrated first by applying the proposed procedure to a few linear vibrating systems for which an alternative solution using adaptive Kalman filter method is possible. Subsequently, illustrative examples on three nonlinear vibrating systems, using synthetic vibration data, are presented to reveal the correct functioning of the method. (c) 2007 Elsevier Ltd. All rights reserved.

Acute Lymphoblastic Leukemia in Adolescents and Young Adults in Finland

In recent reports, adolescents and young adults (AYA) with acute lymphoblastic leukemia (ALL) have had a better outcome with pediatric treatment than with adult protocols. ALL can be classified into biologic subgroups according to immunophenotype and cytogenetics, with different clinical characteristics and outcome. The proportions of the subgroups are different in children and adults. ALL subtypes in AYA patients are less well characterized. In this study, the treatment and outcome of ALL in AYA patients aged 10-25 years in Finland on pediatric and adult protocols was retrospectively analyzed. In total, 245 patients were included. The proportions of biologic subgroups in different age groups were determined. Patients with initially normal or failed karyotype were examined with oligonucleotide microarray-based comparative genomic hybridization (aCGH). Also deletions and instability of chromosome 9p were screened in ALL patients. In addition, patients with other hematologic malignancies were screened for 9p instability. aCGH data were also used to determine a gene set that classifies AYA patients at diagnosis according to their risk of relapse. Receiver operating characteristic analysis was used to assess the value of the set of genes as prognostic classifiers. The 5-year event-free survival of AYA patients treated with pediatric or adult protocols was 67% and 60% (p=0.30), respectively. White blood cell count larger than 100x109/l was associated with poor prognosis. Patients treated with pediatric protocols and assigned to an intermediate-risk group fared significantly better than those of the pediatric high-risk or adult treatment groups. Deletions of 9p were detected in 46% of AYA ALL patients. The chromosomal region 9p21.3 was always affected, and the CDKN2A gene was always deleted. In about 15% of AYA patients, the 9p21.3 deletion was smaller than 200 kb in size, and therefore, probably undetectable with conventional methods. Deletion of 9p was the most common aberration of AYA ALL patients with initially normal karyotype. Instability of 9p, defined as multiple separate areas of copy number loss or homozygous loss within a larger heterozygous area in 9p, was detected in 19% (n=27) of ALL patients. This abnormality was restricted to ALL; none of the patients with other hematologic malignancies had the aberration. The prognostic model identification procedure resulted in a model of four genes: BAK1, CDKN2B, GSTM1, and MT1F. The copy number profile combinations of these genes differentiated between AYA ALL patients at diagnosis depending on their risk of relapse. Deletions of CDKN2B and BAK1 in combination with amplification of GSTM1 and MT1F were associated with a higher probability of relapse. Unlike all previous studies, we found that the outcome of AYA patients with ALL treated using pediatric or adult therapeutic protocols was comparable. The success of adult ALL therapy emphasizes the benefit of referral of patients to academic centers and adherence to research protocols. 9p deletions and instability are common features of ALL and may act together with oncogene-activating translocations in leukemogenesis. New and more sensitive methods of molecular cytogenetics can reveal previously cryptic genetic aberrations with an important role in leukemic development and prognosis and that may be potential targets of therapy. aCGH also provides a viable approach for model design aiming at evaluation of risk of relapse in ALL.

Clinical reasoning: The relative contribution of identification, interpretation and hypothesis errors to misdiagnosis

The aim of this study was to identify and describe the types of errors in clinical reasoning that contribute to poor diagnostic performance at different levels of medical training and experience. Three cohorts of subjects, second- and fourth- (final) year medical students and a group of general practitioners, completed a set of clinical reasoning problems. The responses of those whose scores fell below the 25th centile were analysed to establish the stage of the clinical reasoning process - identification of relevant information, interpretation or hypothesis generation - at which most errors occurred and whether this was dependent on problem difficulty and level of medical experience. Results indicate that hypothesis errors decrease as expertise increases but that identification and interpretation errors increase. This may be due to inappropriate use of pattern recognition or to failure of the knowledge base. Furthermore, although hypothesis errors increased in line with problem difficulty, identification and interpretation errors decreased. A possible explanation is that as problem difficulty increases, subjects at all levels of expertise are less able to differentiate between relevant and irrelevant clinical features and so give equal consideration to all information contained within a case. It is concluded that the development of clinical reasoning in medical students throughout the course of their pre-clinical and clinical education may be enhanced by both an analysis of the clinical reasoning process and a specific focus on each of the stages at which errors commonly occur.

Asteroid identification using statistical orbital inversion methods

An efficient and statistically robust solution for the identification of asteroids among numerous sets of astrometry is presented. In particular, numerical methods have been developed for the short-term identification of asteroids at discovery, and for the long-term identification of scarcely observed asteroids over apparitions, a task which has been lacking a robust method until now. The methods are based on the solid foundation of statistical orbital inversion properly taking into account the observational uncertainties, which allows for the detection of practically all correct identifications. Through the use of dimensionality-reduction techniques and efficient data structures, the exact methods have a loglinear, that is, O(nlog(n)), computational complexity, where n is the number of included observation sets. The methods developed are thus suitable for future large-scale surveys which anticipate a substantial increase in the astrometric data rate. Due to the discontinuous nature of asteroid astrometry, separate sets of astrometry must be linked to a common asteroid from the very first discovery detections onwards. The reason for the discontinuity in the observed positions is the rotation of the observer with the Earth as well as the motion of the asteroid and the observer about the Sun. Therefore, the aim of identification is to find a set of orbital elements that reproduce the observed positions with residuals similar to the inevitable observational uncertainty. Unless the astrometric observation sets are linked, the corresponding asteroid is eventually lost as the uncertainty of the predicted positions grows too large to allow successful follow-up. Whereas the presented identification theory and the numerical comparison algorithm are generally applicable, that is, also in fields other than astronomy (e.g., in the identification of space debris), the numerical methods developed for asteroid identification can immediately be applied to all objects on heliocentric orbits with negligible effects due to non-gravitational forces in the time frame of the analysis. The methods developed have been successfully applied to various identification problems. Simulations have shown that the methods developed are able to find virtually all correct linkages despite challenges such as numerous scarce observation sets, astrometric uncertainty, numerous objects confined to a limited region on the celestial sphere, long linking intervals, and substantial parallaxes. Tens of previously unknown main-belt asteroids have been identified with the short-term method in a preliminary study to locate asteroids among numerous unidentified sets of single-night astrometry of moving objects, and scarce astrometry obtained nearly simultaneously with Earth-based and space-based telescopes has been successfully linked despite a substantial parallax. Using the long-term method, thousands of realistic 3-linkages typically spanning several apparitions have so far been found among designated observation sets each spanning less than 48 hours.

Identification of Hadronically Decaying Tau Leptons in Searches for Heavy MSSM Higgs Bosons with the CMS Detector at the CERN LHC

This thesis describes methods for the reliable identification of hadronically decaying tau leptons in the search for heavy Higgs bosons of the minimal supersymmetric standard model of particle physics (MSSM). The identification of the hadronic tau lepton decays, i.e. tau-jets, is applied to the gg->bbH, H->tautau and gg->tbH+, H+->taunu processes to be searched for in the CMS experiment at the CERN Large Hadron Collider. Of all the event selections applied in these final states, the tau-jet identification is the single most important event selection criterion to separate the tiny Higgs boson signal from a large number of background events. The tau-jet identification is studied with methods based on a signature of a low charged track multiplicity, the containment of the decay products within a narrow cone, an isolated electromagnetic energy deposition, a non-zero tau lepton flight path, the absence of electrons, muons, and neutral hadrons in the decay signature, and a relatively small tau lepton mass compared to the mass of most hadrons. Furthermore, in the H+->taunu channel, helicity correlations are exploited to separate the signal tau jets from those originating from the W->taunu decays. Since many of these identification methods rely on the reconstruction of charged particle tracks, the systematic uncertainties resulting from the mechanical tolerances of the tracking sensor positions are estimated with care. The tau-jet identification and other standard selection methods are applied to the search for the heavy neutral and charged Higgs bosons in the H->tautau and H+->taunu decay channels. For the H+->taunu channel, the tau-jet identification is redone and optimized with a recent and more detailed event simulation than previously in the CMS experiment. Both decay channels are found to be very promising for the discovery of the heavy MSSM Higgs bosons. The Higgs boson(s), whose existence has not yet been experimentally verified, are a part of the standard model and its most popular extensions. They are a manifestation of a mechanism which breaks the electroweak symmetry and generates masses for particles. Since the H->tautau and H+->taunu decay channels are important for the discovery of the Higgs bosons in a large region of the permitted parameter space, the analysis described in this thesis serves as a probe for finding out properties of the microcosm of particles and their interactions in the energy scales beyond the standard model of particle physics.

Impact of a new mandatory reporting law on reporting and identification of child sexual abuse: A seven year time trend analysis

Child sexual abuse is widespread and difficult to detect. To enhance case identification, many societies have enacted mandatory reporting laws requiring designated professionals, most often police, teachers, doctors and nurses, to report suspected cases to government child welfare agencies. Little research has explored the effects of introducing a reporting law on the number of reports made, and the outcomes of those reports. This study explored the impact of a new legislative mandatory reporting duty for child sexual abuse in the State of Western Australia over seven years. We analysed data about numbers and outcomes of reports by mandated reporters, for periods before the law (2006-08) and after the law (2009-12). Results indicate that the number of reports by mandated reporters of suspected child sexual abuse increased by a factor of 3.7, from an annual mean of 662 in the three year pre-law period to 2448 in the four year post-law period. The increase in the first two post-law years was contextually and statistically significant. Report numbers stabilised in 2010-12, at one report per 210 children. The number of investigated reports increased threefold, from an annual mean of 451 in the pre-law period to 1363 in the post-law period. Significant decline in the proportion of mandated reports that were investigated in the first two post-law years suggested the new level of reporting and investigative need exceeded what was anticipated. However, a subsequent significant increase restored the pre-law proportion, suggesting systemic adaptive capacity. The number of substantiated investigations doubled, from an annual mean of 160 in the pre-law period to 327 in the post-law period, indicating twice as many sexually abused children were being identified.

Identification of protein interaction regions of VINC/NEAT1/Men epsilon RNA

The virus inducible non-coding RNA (VINC) was detected initially in the brain of mice infected with Japanese encephalitis virus (JEV) and rabies virus. VINC is also known as NEAT1 or Men epsilon RNA. It is localized in the nuclear paraspeckles of several murine as well as human cell lines and is essential for paraspeckle formation. We demonstrate that VINC interacts with the paraspeckle protein, P54nrb through three different protein interaction regions (PIRs) one of which (PIR-1) is localized near the 50 end while the other two (PIR-2, PIR-3) are localized near the 30 region of VINC. Our studies suggest that VINC may interact with P54nrb through a novel mechanism which is different from that reported for protein coding RNAs. (C) 2010 Federation of European Biochemical Societies. Published by Elsevier B. V. All rights reserved.

Proteomic identification of putative microRNA394 target genes in Arabidopsis thaliana identifies MLP family members critical for normal development

Expression of the F-Box protein Leaf Curling Responsiveness (LCR) is regulated by microRNA, miR394, and alterations to this interplay in Arabidopsis thaliana produce defects in leaf polarity and shoot apical meristem (SAM) organisation. Although the miR394-LCR node has been documented in Arabidopsis, the identification of proteins targeted by LCR F-box itself has proven problematic. Here, a proteomic analysis of shoot apices from plants with altered LCR levels identified a member of the Major Latex Protein (MLP) family gene as a potential LCR F-box target. Bioinformatic and molecular analyses also suggested that other MLP family members are likely to be targets for this post-translational regulation. Direct interaction between LCR F-Box and MLP423 was validated. Additional MLP members had reduction in protein accumulation, in varying degrees, mediated by LCR F-Box. Transgenic Arabidopsis lines, in which MLP28 expression was reduced through an artificial miRNA technology, displayed severe developmental defects, including changes in leaf patterning and morphology, shoot apex defects, and eventual premature death. These phenotypic characteristics resemble those of Arabidopsis plants modified to over-express LCR. Taken together, the results demonstrate that MLPs are driven to degradation by LCR, and indicate that MLP gene family is target of miR394-LCR regulatory node, representing potential targets for directly post-translational regulation mediated by LCR F-Box. In addition, MLP28 family member is associated with the LCR regulation that is critical for normal Arabidopsis development.

Sequencing of T-superfamily conotoxins from Conus virgo: Pyroglutamic acid identification and disulfide arrangement by MALDI mass spectrometry

De novo mass spectrometric sequencing of two Conus peptides, Vi1359 and Vi1361, from the vermivorous cone snail Conus virgo, found off the southern Indian coast, is presented. The peptides, whose masses differ only by 2 Da, possess two disulfide bonds and an amidated C-terminus. Simple chemical modifications and enzymatic cleavage coupled with matrix assisted laser desorption ionization (MALDI) mass spectrometric analysis aided in establishing the sequences of Vi1359, ZCCITIPECCRI-NH2, and Vi1361, ZCCPTMPECCRI-NH2, Which differ only at residues 4 and 6 (Z = pyroglutamic acid). The presence of the pyroglutamyl residue at the N-terminus was unambiguously identified by chemical hydrolysis of the cyclic amide, followed by esterification. The presence of Ile residues in both the peptides was confirmed from high-energy collision induced dissociation (CID) studies, using the observation Of W-n- and d(n)-ions as a diagnostic. Differential cysteine labeling, in conjunction with MALDI-MS/MS, permitted establishment of disulfide connectivity in both peptides as Cys2-Cys9 and Cys3-Cys10. The cysteine pattern clearly reveals that the peptides belong to the class of T-superfamily conotoxins, in particular the T-1 superfamily.

Identification and characterization of a library of microheterogeneous cyclohexadepsipeptides from the fungus Isaria

Ten new cyclic hexadepsipeptides, six isariins and four isaridins, from the fungus Isaria have been identified and characterized by high-performance liquid chromatography, coupled to tandem electrospray ionization mass spectrometry (LC-ESIMS/MS). The isariins possess a beta-hydroxy acid residue and five alpha-amino acids, while isaridins contain a beta-amino acid, an alpha-hydroxy acid, and four alpha-amino acids. One- and two-dimensional NMR spectroscopy confirmed the chemical identity of some of the isariin fractions. Mass spectral fragmentation patterns of [M + H](+) ions reveal clear diagnostic fragment ions for the isariins and isaridins. Previously described cyclic depsipeptides, isarfelins from Isaria felina (Guo, Y. X.; Liu, Q. H.; Ng, T. B.; Wang H. X. Peptides 2005, 26, 2384), are now reassigned as members of the isaridin family. Examination of isaridin sequences revealed significant similarities with cyclic hexadepsipeptides such as destruxins and roseotoxins. The structure of an isariin (isariin A) investigated by NMR spectroscopy indicated the presence of a hybrid alpha beta C-11 turn, formed by the beta-hydroxy acid and glycine residues and a (D)Leu-(L)Ala type II' beta-turn. Additionally, the inhibitory effect of isariins and an isaridin on the intra-erythrocytic growth of Plasmodium falciparum is presented.

Mass Spectrometry-Based Systems Approach for Identification of Inhibitors of Plasmodium falciparum Fatty Acid Synthase{triangledown}

The emergence of strains of Plasmodium falciparum resistant to the commonly used antimalarials warrants the development of new antimalarial agents. The discovery of type II fatty acid synthase (FAS) in Plasmodium distinct from the FAS in its human host (type I FAS) opened up new avenues for the development of novel antimalarials. The process of fatty acid synthesis takes place by iterative elongation of butyryl-acyl carrier protein (butyryl-ACP) by two carbon units, with the successive action of four enzymes constituting the elongation module of FAS until the desired acyl length is obtained. The study of the fatty acid synthesis machinery of the parasite inside the red blood cell culture has always been a challenging task. Here, we report the in vitro reconstitution of the elongation module of the FAS of malaria parasite involving all four enzymes, FabB/F (β-ketoacyl-ACP synthase), FabG (β-ketoacyl-ACP reductase), FabZ (β-ketoacyl-ACP dehydratase), and FabI (enoyl-ACP reductase), and its analysis by matrix-assisted laser desorption-time of flight mass spectrometry (MALDI-TOF MS). That this in vitro systems approach completely mimics the in vivo machinery is confirmed by the distribution of acyl products. Using known inhibitors of the enzymes of the elongation module, cerulenin, triclosan, NAS-21/91, and (–)-catechin gallate, we demonstrate that accumulation of intermediates resulting from the inhibition of any of the enzymes can be unambiguously followed by MALDI-TOF MS. Thus, this work not only offers a powerful tool for easier and faster throughput screening of inhibitors but also allows for the study of the biochemical properties of the FAS pathway of the malaria parasite.

Mass Spectrometry-Based Systems Approach for Identification of Inhibitors of Plasmodium falciparum Fatty Acid Synthase{triangledown}

The emergence of strains of Plasmodium falciparum resistant to the commonly used antimalarials warrants the development of new antimalarial agents. The discovery of type II fatty acid synthase (FAS) in Plasmodium distinct from the FAS in its human host (type I FAS) opened up new avenues for the development of novel antimalarials. The process of fatty acid synthesis takes place by iterative elongation of butyryl-acyl carrier protein (butyryl-ACP) by two carbon units, with the successive action of four enzymes constituting the elongation module of FAS until the desired acyl length is obtained. The study of the fatty acid synthesis machinery of the parasite inside the red blood cell culture has always been a challenging task. Here, we report the in vitro reconstitution of the elongation module of the FAS of malaria parasite involving all four enzymes, FabB/F (β-ketoacyl-ACP synthase), FabG (β-ketoacyl-ACP reductase), FabZ (β-ketoacyl-ACP dehydratase), and FabI (enoyl-ACP reductase), and its analysis by matrix-assisted laser desorption-time of flight mass spectrometry (MALDI-TOF MS). That this in vitro systems approach completely mimics the in vivo machinery is confirmed by the distribution of acyl products. Using known inhibitors of the enzymes of the elongation module, cerulenin, triclosan, NAS-21/91, and (–)-catechin gallate, we demonstrate that accumulation of intermediates resulting from the inhibition of any of the enzymes can be unambiguously followed by MALDI-TOF MS. Thus, this work not only offers a powerful tool for easier and faster throughput screening of inhibitors but also allows for the study of the biochemical properties of the FAS pathway of the malaria parasite.

Amino acid sequence of the winged bean (Psophocarpus tetragonolobus) basic lectin. Adenine binding and identification of the active-site tryptophan residue

The complete amino acid sequence of winged bean basic agglutinin (WBA I) was obtained by a combination of manual and gas-phase sequencing methods. Peptide fragments for sequence analyses were obtained by enzymatic cleavages using trypsin and Staphylococcus aureus V8 endoproteinase and by chemical cleavages using iodosobenzoic acid, hydroxylamine, and formic acid. COOH-terminal sequence analysis of WBA I and other peptides was performed using carboxypeptidase Y. The primary structure of WBA I was homologous to those of other legume lectins and more so to Erythrina corallodendron. Interestingly, the sequence shows remarkable identities in the regions involved in the association of the two monomers of E. corallodendron lectin. Other conserved regions are the double metal-binding site and residues contributing to the formation of the hydrophobic cavity and the carbohydrate-binding site. Chemical modification studies both in the presence and absence of N-acetylgalactosamine together with sequence analyses of tryptophan-containing tryptic peptides demonstrate that tryptophan 133 is involved in the binding of carbohydrate ligands by the lectin. The location of tryptophan 133 at the active center of WBA I for the first time subserves to explain a role for one of the most conserved residues in legume lectins.

Identification of carbohydrate structures as receptors for localised adherent enteropathogenic Escherichia coli

Enteropathogenic Escherichia coli strains of diffused adherent (DA) and localised adherent (LA) phenotypes were tested for their ability to bind to glycolipids. DA strains did not bind to the glycolipids tested, while LA strains bound to asialo GM1, asialo GM2, globoside and lacto-N-neotetraose in decreasing order of avidity. The minimum common sequence among the four glycolipids could be delineated as GalNac β 1–4 Gal as the binding epitope with GalNac β 1–3 Gal and GlcNac β 1–3 Gal serving as relatively weaker binders. The binding was not inhibited by a variety of free oligosaccharides or by the neoglycoproteins tested. Adhesion-negative mutants of an enteropathogenic LA strain showed a markedly reduced binding to asialo GM1 indicating that the recognition of GalNac β 1–4 Gal was correlated with the ability to adhere to HeLa cells. Thus recognition and binding to glycolipids could play an important role in colonisation through adherence to intestinal surfaces.