bluuebunny/crossref_metadata_2025_split huggingface dataset:
A suffix tree approach to the interpretation of tandem mass
spectra: applications to peptides of non-specific digestion and
post-translational modifications
Authors: Lu Bingwen , Chen Ting 
Published: October 2003

Abstract
Motivation: Tandem mass spectrometry combined with sequence database searching is one of the most powerful tools for protein identification. As thousands of spectra are generated by a mass spectrometer in one hour, the speed of database searching is critical, especially when searching against a large sequence database, or when the peptide is generated by some unknown or non-specific enzyme, even or when the target peptides have post-translational modifications (PTM). In practice, about 70–90% of the spectra have no match in the database. Many believe that a significant portion of them are due to peptides of non-specific digestions by unknown enzymes or amino acid modifications. In another case, scientists may choose to use some non-specific enzymes such as pepsin or thermolysin for proteolysis in proteomic study, in that not all proteins are amenable to be digested by some site-specific enzymes, and furthermore many digested peptides may not fall within the rang of molecular weight suitable for mass spectrometry analysis. Interpretating mass spectra of these kinds will cost a lot of computational time of database search engines.
Overview: The present study was designed to speed up the database searching process for both cases. More specifically speaking, we employed an approach combining suffix tree data structure and spectrum graph. The suffix tree is used to preprocess the protein sequence database, while the spectrum graph is used to preprocess the tandem mass spectrum. We then search the suffix tree against the spectrum graph for candidate peptides. We design an efficient algorithm to compute a matching threshold with some statistical significance level, e.g. p = 0.01, for each spectrum, and use it to select candidate peptides. Then we rank these peptides using a SEQUEST-like scoring function. The algorithms were implemented and tested on experimental data. For post-translational modifications, we allow arbitrary number of any modification to a protein.
Availability: The executable program and other supplementary materials are available online at: http://hto-c.usc.edu:8000/msms/suffix/.
Contact: tingchen@hto.usc.edu
*To whom correspondence should be addressed.
The shortest common supersequence problem in a microarray production setting
Authors: Rahmann Sven 
Published: October 2003

Abstract
Motivation: During microarray production, several thousands of oligonucleotides (short DNA sequences) are synthesized in parallel, one nucleotide at a time. We are interested in finding the shortest possible nucleotide deposition sequence to synthesize all oligos in order to reduce production time and increase oligo quality. Thus we study the shortest common supersequence problem of several thousand short strings over a four-letter alphabet.
Results: We present a statistical analysis of the basic Alphabet-Leftmostapproximation algorithm, and propose several practical heuristics to reduce the length of the supersequence. Our results show that it is hard to beat Alphabet-Leftmostin the microarray production setting by more than 2 characters, but these savings can improve overall oligo quality by more than four percent.
Availability: Source code in C may be obtained by contacting the author, or from http://oligos.molgen.mpg.de.
Contact: Sven.Rahmann@molgen.mpg.de
A description of dynamical graphs associated to elementary
regulatory circuits
Authors: Remy E. , Mossé B. , Chaouiya C. , Thieffry D. 
Published: October 2003

Abstract
The biological and dynamical importance of feedback circuits in regulatory graphs has often been emphasized. The work presented here aims at completly describing the dynamics of isolated elementary regulatory circuits. Our analytical approach is based on a discrete formal framework, built upon the logical approach of R. Thomas.
Given a regulatory circuit, we show that the structure of synchronous and asynchronous dynamical graphs depends only on the length of the circuit (number of genes) and on its sign (which depends on the parity of the number of negative interactions). This work constitutes a first step towards the analytical characterisation of discrete dynamical graphs for more complex regulatory networks in terms of contributions corresponding to their embedded elementary circuits.
Contact: remy@iml.univ-mrs.fr
*To whom correspondence should be addressed.
Biclustering microarray data by Gibbs sampling
Authors: Sheng Qizheng , Moreau Yves , De Moor Bart 
Published: October 2003

Abstract
Motivation: Gibbs sampling has become a method of choice for the discovery of noisy patterns, known as motifs, in DNA and protein sequences. Because handling noise in microarray data presents similar challenges, we have adapted this strategy to the biclustering of discretized microarray data.
Results: In contrast with standard clustering that reveals genes that behave similarly over all the conditions, biclustering groups genes over only a subset of conditions for which those genes have a sharp probability distribution. We have opted for a simple probabilistic model of the biclusters because it has the key advantage of providing a transparent probabilistic interpretation of the biclusters in the form of an easily interpretable fingerprint. Furthermore, Gibbs sampling does not suffer from the problem of local minima that often characterizes Expectation–Maximization. We demonstrate the effectiveness of our approach on two synthetic data sets as well as a data set from leukemia patients.
Contact: qizheng.sheng@esat.kuleuven.ac.be
*To whom correspondence should be addressed.
Sterol glucosyltransferases have different functional roles inPichia pastoris and Yarrowia lipolytica
Authors: Stasyk Oleh V , Nazarko Taras Y , Stasyk Olena G , Krasovska Olena S , Warnecke Dirk , Nicaud Jean‐Marc , Cregg James M , Sibirny Andrei A 
Published: October 2003

AbstractMutants of the methanol‐utilizing yeast Pichia pastoris and the alkane‐utilizing yeast Yarrowia lipolytica defective in the orthologue of UGT51 (encoding sterol glucosyltransferase) were isolated and compared. These mutants do not contain the specific ergosterol derivate, ergosterol glucoside. We observed that the P. pastoris UGT51 gene is required for pexophagy, the process by which peroxisomes containing methanol‐metabolizing enzymes are selectively shipped to and degraded in the vacuole upon shifting methanol‐grown cells of this yeast to glucose or ethanol. PpUGT51 is also required for other vacuole related processes. In contrast, the Y. lipolytica UGT51 gene is required for utilization of decane, but not for pexophagy. Thus, sterol glucosyltransferases play different functional roles in P. pastoris and Y. lipolytica.
Intramembranous ossification mechanism for bone bridge formation at the growth plate cartilage injury site
Authors: Xian Cory J. , Zhou Fiona H. , McCarty Rosa C. , Foster Bruce K. 
Published: October 2003

AbstractSalter's type III and type IV growth plate injuries often induce bone bridge formation at the injury site. To understand the cellular mechanisms, this study characterized proximal tibial transphyseal injury in rats. Histologically, bony bridge trabeculae appeared on day 7, increased on day 10, and became well‐constructed on day 14 with marrow. Prior to and during bone bridging, there was no cartilage proteoglycan metachromatic staining and no collagen‐X immunostaining at the injury site, nor was there any up‐regulation of BrdU‐labelled chondrocyte proliferation at the adjacent physeal cartilage, suggesting no new cartilage formation at the injury site. However, infiltration of vimentin‐immunopositive mesenchymal cells from metaphysis and epiphysis was apparent on day 3, with the mesenchymal population being prominent on days 7 and 10 and subsided on day 14. Among these infiltrates were osteoprogenitor precursors expressing osteoblast differentiation factor (cbf‐α1) on day 3, along with some cbf‐α1° osteoblast‐like cells lining bone trabeculae on days 7 and 10. Some mesenchymal cells and trabecula‐lining cells were also alkaline phosphatase‐immunopositive, further suggesting their osteoblast differentiation. From day 7 onwards, some trabecula‐lining cells became osteocalcin‐producing mature osteoblasts. These results suggest that bone bridge formation after growth plate injury occurs directly via intramembranous ossification through recruitment of marrow‐derived osteoprogenitor cells. © 2003 Orthopaedic Research Society. Published by Elsevier Ltd. All rights reserved.
Early osteoblastic differentiation induced by dexamethasone enhances adenoviral gene delivery to marrow stromal cells
Authors: Blum Jeremy S. , Parrott M. Brandon , Mikos Antonios G. , Barry Michael A. 
Published: October 2003

AbstractWe investigated the implications of induced osteogenic differentiation on gene delivery in multipotent rat marrow stromal cells (MSCs). Prior to genetic manipulation cells were cultured with or without osteogenic supplements (5 ± 10−8 M dexamethasone, 160 μM l‐ascorbic acid 2‐phosphate, and 10 mM β‐glycerophosphate). Comparison of liposome, retroviral, and adenoviral vectors demonstrated that all three vectors could mediate gene delivery to primary rat MSCs. When these vectors were applied in the absence or presence of osteogenic supplements, we found that MSCs differentiated prior to transduction with adenovirus type 5 vectors produced a 300% increase in transgene expression compared to MSCs that were not exposed to osteogenic supplements. This differentiation effect appeared specific to adenoviral mediated gene delivery, since there was minimal increase in retroviral gene delivery and no increase in liposome gene delivery when MSCs were treated with osteogenic supplements. In addition, we also determined this increase in transgene production to occur at a higher concentration of dexamethasone (5 ± 10−8 M) in the culture medium of MSCs prior to adenoviral transduction. We found that this increased transgene production could be extended to the osteogenic protein, human bone morphogenetic protein 2 (hBMP‐2). When delivered by an adenoviral vector, hBMP‐2 transgene production could be increased from 1.4 ng/105 cells/3 days to 4.3 ng/105 cells/3 days by culture of MSCs with osteogenic supplements prior to transduction. These results indicate that the utility of MSCs as a therapeutic protein delivery mechanism through genetic manipulation can be enhanced by pre‐culture of these cells with dexamethasone. © 2003 Orthopaedic Research Society. Published by Elsevier Ltd. All rights reserved.
A statistical approach to evaluating distance metrics and analog assignments for pollen records
Authors: Gavin Daniel G , Oswald W.Wyatt , Wahl Eugene R , Williams John W 
Published: October 2003

AbstractThe modern analog technique typically uses a distance metric to determine the dissimilarity between fossil and modern biological assemblages. Despite this quantitative approach, interpretation of distance metrics is usually qualitative and rules for selection of analogs tend to bead hoc. We present a statistical tool, the receiver operating characteristic (ROC) curve, which provides a framework for identifying analogs from distance metrics. If modern assemblages are placed into groups (e.g., biomes), this method can (1) evaluate the ability of different distance metrics to distinguish among groups, (2) objectively identify thresholds of the distance metric for determining analogs, and (3) compute a likelihood ratio and a Bayesian probability that a modern group is an analog for an unknown (fossil) assemblage. Applied to a set of 1689 modern pollen assemblages from eastern North America classified into eight biomes, ROC analysis confirmed that the squared-chord distance (SCD) outperforms most other distance metrics. The optimal threshold increased when more dissimilar biomes were compared. The probability of an analog vs no-analog result (a likelihood ratio) increased sharply when SCD decreased below the optimal threshold, indicating a nonlinear relationship between SCD and the probability of analog. Probabilities of analog computed for a postglacial pollen record at Tannersville Bog (Pennsylvania, USA) identified transitions between biomes and periods of no analog.
Sensitivity of lysosomal enzymes to the plant alkaloid sanguinarine: comparison with other SH‐specific agents
Authors: Belyaeva T. , Leontieva E. , Shpakov A. , Mozhenok T. , Faddejeva M. 
Published: October 2003

AbstractThe influence of the benzo[c]phenanthridine alkaloid sanguinarine on some lysosomal enzyme activities was investigated. Sanguinarine inhibits lysosomal hydrolases in homogenates of cultured mouse fibroblasts. After incubation of mouse fibroblasts in culture with 100 μM sanguinarine an approximately 50% decrease in the activities of N‐acetyl‐β,d‐glucosaminidase (NAGA), β‐galactosidase (GAL), arylsulfatase and acid lipase was observed. Because the biological activity of sanguinarine might arise from the interaction of its iminium cation with enzyme thiol groups, we compared its effect on NAGA, GAL and acid phosphatase (AcP) activities with the effects of SH‐specific reagents p‐chloromercuribenzoic acid (CPMA) and N‐ethylmaleimide (NEM). Treatment of lysosomal fractions with millimolar concentrations of sanguinarine induces a dose‐dependent inhibition of the enzymes; for example, 0.6 mM sanguinarine causes approximately a 40% decrease in AcP and NAGA activities. NEM has similar effects, and increasing the preincubation temperature from 0 °C to 37 °C intensifies the inhibition due to both agents. CPMA also inhibits the activity of GAL (IC500.7 μM), AcP (IC5012.5 μM) and NAGA (IC506.8 μM) in a dose‐dependent manner but is more potent than sanguinarine or NEM. Comparative analysis of the primary structures of these enzymes using the program BLAST reveals the presence of highly conserved cysteine residues, which confirms the importance of thiol‐groups for their activities. Thus, both the experimental observations obtained in this study and the literature data imply a significant role of redox‐based mechanisms in regulating lysosomal functional activity.
The effects of acute afterload change on systolic ventricular function in conscious dogs with normal vs. failing hearts
Authors: Thompson Richard B. , van den Bos Ewout J. , Esposito David J. , Owen Clarence H. , Glower Donald D. 
Published: October 2003

AbstractBackground:To date, no data exist on the linearity and, therefore, the usefulness of the preload recruitable stroke work (PRSW) and end‐systolic pressure–volume (ESPVR) relationships during acute afterload changes in heart failure.Aims:Our aim was, therefore, to characterize both relationships in a model of ventricular pacing induced heart failure at baseline and during acute changes in afterload.Methods:Dynamic left ventricular volume and transmural pressure were measured in 10 conscious dogs using sonomicrometry and micromanometry under control conditions and during heart failure produced by 3 weeks of rapid right ventricular pacing. Afterload was varied from baseline with intravenous infusions of nitroprusside and phenylephrine. Left ventricular function was assessed using the PRSW and ESPVR relationships.Results:Cardiac output demonstrated a linear inverse relationship with afterload in both normal and failing hearts (r2>0.5, P<0.001) with failure producing a parallel, downward shift of the afterload (x) vs. cardiac output (y) relationship (P<0.01). Yet, afterload variation did not affect PRSW or ESPVR relationships in either normal or failing hearts (r2<0.12, P>0.05).Conclusion:Thus, the PRSW and ESPVR relationships are insensitive to acute afterload changes in both failing and normal hearts, and the failing left ventricle is no more afterload‐sensitive than the normal heart.
The Lessons of Defeat: Transforming the Qing State after the Boxer War
Authors: Thompson Roger R. 
Published: October 2003

These four essays were first presented to an audience in Washington, D.C. in April 2002 at the Annual Meeting of the Association for Asian Studies. Richard Horowitz, the panel organizer, argued that:the roots of China's modern state can be found in the Xinzheng or ‘new policy’ reforms during the last decade of the Qing dynasty. These reforms marked a radical departure for the Chinese state, involving a sustained effort to import foreign models and adapt them to Chinese realities. Although scholarship on reforms to provincial and local state institutions in this period is substantial, the transformation of the central government in Beijing has received little attention.
Searching for statistically significant regulatory modules
Authors: Bailey Timothy L. , Noble William Stafford 
Published: October 2003

Abstract
Motivation: The regulatory machinery controlling gene expression is complex, frequently requiring multiple, simultaneous DNA-protein interactions. The rate at which a gene is transcribed may depend upon the presence or absence of a collection of transcription factors bound to the DNA near the gene. Locating transcription factor binding sites in genomic DNA is difficult because the individual sites are small and tend to occur frequently by chance. True binding sites may be identified by their tendency to occur in clusters, sometimes known as regulatory modules.
Results: We describe an algorithm for detecting occurrences of regulatory modules in genomic DNA. The algorithm, called mcast, takes as input a DNA database and a collection of binding site motifs that are known to operate in concert. mcast uses a motif-based hidden Markov model with several novel features. The model incorporates motif-specific p-values, thereby allowing scores from motifs of different widths and specificities to be compared directly. The p-value scoring also allows mcast to only accept motif occurrences with significance below a user-specified threshold, while still assigning better scores to motif occurrences with lower p-values. mcast can search long DNA sequences, modeling length distributions between motifs within a regulatory module, but ignoring length distributions between modules. The algorithm produces a list of predicted regulatory modules, ranked by E-value. We validate the algorithm using simulated data as well as real data sets from fruitfly and human.
Availability: http://meme.sdsc.edu/MCAST/paper
Contact: tlb@maths.uq.edu.au
*To whom correspondence should be addressed.
†Formerly William Noble Grundy, see www.gs.washington.edu/noble/name-change.html
HMM sampling and applications to gene finding and alternative
splicing
Authors: Cawley Simon L. , Pachter Lior 
Published: October 2003

Abstract
The standard method of applying hidden Markov models to biological problems is to find a Viterbi (maximal weight) path through the HMM graph. The Viterbi algorithm reduces the problem of finding the most likely hidden state sequence that explains given observations, to a dynamic programming problem for corresponding directed acyclic graphs. For example, in the gene finding application, the HMM is used to find the most likely underlying gene structure given a DNA sequence. In this note we discuss the applications of sampling methods for HMMs. The standard sampling algorithm for HMMs is a variant of the common forward-backward and backtrack algorithms, and has already been applied in the context of Gibbs sampling methods. Nevetheless, the practice of sampling state paths from HMMs does not seem to have been widely adopted, and important applications have been overlooked. We show how sampling can be used for finding alternative splicings for genes, including alternative splicings that are conserved between genes from related organisms. We also show how sampling from the posterior distribution is a natural way to compute probabilities for predicted exons and gene structures being correct under the assumed model. Finally, we describe a new memory efficient sampling algorithm for certain classes of HMMs which provides a practical sampling alternative to the Hirschberg algorithm for optimal alignment. The ideas presented have applications not only to gene finding and HMMs but more generally to stochastic context free grammars and RNA structure prediction.
Key words: suboptimal parses, sampling, hidden Markov model, conserved alternative splicing
Contact: lpachter@math.berkeley.edu
*To whom correspondence should be addressed.
Divide-and-conquer multiple alignment with segment-based
constraints
Authors: Sammeth Michael , Morgenstern Burkhard , Stoye Jens 
Published: October 2003

Abstract
A large number of methods for multiple sequence alignment are currenty available. Recent benchmarking tests demonstrated that strengths and drawbacks of these methods differ substantially. Global strategies can be outperformed by approaches based on local similarities and vice versa, depending on the characteristics of the input sequences. In recent years, mixed approaches that include both global and local features have shown promising results. Herein, we introduce a new algorithm for multiple sequence alignment that integrates the global divide-and-conquer approach with the local segment-based approach, thereby combining the strengths of those two strategies.
Contact: micha@sammeth.net
*To whom correspondence should be addressed.
Gene prediction with a hidden Markov model and a new intron
submodel
Authors: Stanke Mario , Waack Stephan 
Published: October 2003

Abstract
Motivation: The problem of finding the genes in eukaryotic DNA sequences by computational methods is still not satisfactorily solved. Gene finding programs have achieved relatively high accuracy on short genomic sequences but do not perform well on longer sequences with an unknown number of genes in them. Here existing programs tend to predict many false exons.
Results: We have developed a new program, AUGUSTUS, for the ab initio prediction of protein coding genes in eukaryotic genomes. The program is based on a Hidden Markov Model and integrates a number of known methods and submodels. It employs a new way of modeling intron lengths. We use a new donor splice site model, a new model for a short region directly upstream of the donor splice site model that takes the reading frame into account and apply a method that allows better GC-content dependent parameter estimation. AUGUSTUS predicts on longer sequences far more human and drosophila genes accurately than the ab initio gene prediction programs we compared it with, while at the same time being more specific.
Availability: A web interface for AUGUSTUS and the executable program are located at http://augustus.gobics.de.
Supplementary Information: The datasets used for testing and training are available at http://augustus.gobics.de/datasets/
Contact: mstanke@gwdg.de
*To whom correspondence should be addressed.
Extracting active pathways from gene expression data
Authors: Vert Jean Philippe , Kanehisa Minoru 
Published: October 2003

Abstract
Motivation: A promising way to make sense out of gene expression profiles is to relate them to the activity of metabolic and signalling pathways. Each pathway usually involves many genes, such as enzymes, which can themselves participate in many pathways. The set of all known pathways can therefore be represented by a complex network of genes. Searching for regularities in the set of gene expression profiles with respect to the topology of this gene network is a way to automatically extract active pathways and their associated patterns of activity.
Method: We present a method to perform this task, which consists in encoding both the gene network and the set of profiles into two kernel functions, and performing a regularized form of canonical correlation analysis between the two kernels.
Results: When applied to publicly available expression data the method is able to extract biologically relevant expression patterns, as well as pathways with related activity.
Contact: Jean-Philippe.Vert@mines.org
*To whom corespondence should be addressed.