bluuebunny/crossref_metadata_2025_split huggingface dataset:
Interpolated markov chains for eukaryotic promoter recognition.
Authors: Ohler U , Harbeck S , Niemann H , N√∂th E , Reese M G 
Published: July 2002

Abstract
MOTIVATION: We describe a new content-based approach for the detection of promoter regions of eukaryotic protein encoding genes. Our system is based on three interpolated Markov chains (IMCs) of different order which are trained on coding, non-coding and promoter sequences. It was recently shown that the interpolation of Markov chains leads to stable parameters and improves on the results in microbial gene finding (Salzberg et al., Nucleic Acids Res., 26, 544-548, 1998). Here, we present new methods for an automated estimation of optimal interpolation parameters and show how the IMCs can be applied to detect promoters in contiguous DNA sequences. Our interpolation approach can also be employed to obtain a reliable scoring function for human coding DNA regions, and the trained models can easily be incorporated in the general framework for gene recognition systems. RESULTS: A 5-fold cross-validation evaluation of our IMC approach on a representative sequence set yielded a mean correlation coefficient of 0.84 (promoter versus coding sequences) and 0.53 (promoter versus non-coding sequences). Applied to the task of eukaryotic promoter region identification in genomic DNA sequences, our classifier identifies 50% of the promoter regions in the sequences used in the most recent review and comparison by Fickett and Hatzigeorgiou ( Genome Res., 7, 861-878, 1997), while having a false-positive rate of 1/849 bp.
Complete genomes in WWW Entrez: data representation and analysis.
Authors: Tatusova T A , Karsch-Mizrachi I , Ostell J A 
Published: July 2002

Abstract
MOTIVATION: The large amount of genome sequence data now publicly available can be accessed through the National Center for Biotechnology Information (NCBI) Entrez search and retrieval system, making it possible to explore data of a breadth and scope exceeding traditional flatfile views. RESULTS: Here we report recent improvements for completely sequenced genomes from viruses, bacteria, and yeast. Flexible web based views, precomputed relationships, and immediate access to analytical tools provide scientists with a portal into the new insights to be gained from completed genome sequences. AVAILABILITY: Entrez Genomes can be accessed on the World Wide Web at http://www.ncbi.nlm.nih.gov/Entrez/Genome/ org.html.
POWER_SAGE: comparing statistical tests for SAGE experiments
Authors: Man Michael Z. , Wang Xuning , Wang Yixin 
Published: July 2002

Abstract
Motivation: The Serial Analysis of Gene Expression (SAGE) technology determines the expression level of a gene by measuring the frequency of a sequence tag derived from the corresponding mRNA transcript. Several statistical tests have been developed to detect significant differences in tag frequency between two samples. However, which one of these tests has the greatest power to detect real changes remains undetermined.
Results: This paper compares three statistical tests for detecting significant changes of gene expression in SAGE experiments. The comparison makes use of Monte Carlo simulation that, in essence, generates ‘virtual’ SAGE experiments. Our analysis shows that the Chi-square test has the best power and robustness. Since the POWER_ SAGE program can easily run ‘virtual’ SAGE studies with different combinations of sample size and tag frequency and determine the power for each combination, it can serve as a useful tool for planning SAGE experiments.
Availability: The POWER_ SAGE software is available upon request from the authors.
Contact: michael.man@pfizer.com
To whom correspondence should be addressed.
Comparing systemic properties of ensembles of biological
networks by graphical and statistical methods
Authors: Alves Rui , Savageau Michael A. 
Published: July 2002

Abstract
Motivation: When dealing with questions that concern a general class of models for biological networks, large numbers of distinct models within the class can be grouped into an ensemble that gives a statistical view of the properties for the general class. Comparing properties of different ensembles through the use of point measures (e.g. medians, standard deviations, correlation coefficients) can mask inhomogeneities in the correlations between properties. We are therefore motivated to develop strategies that allow these inhomogeneities to be more easily detected.
Results: Methods are described for constructing ensembles of models within the context of a Mathematically Controlled Comparison. A Density of Ratios Plot for a given systemic property is then defined as follows: the \batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \(y\) \end{document}axis represents the value of the systemic property in a reference model divided by the value in the alternative model, and the \batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \(x\) \end{document}axis represents the value of the systemic property in the reference model. Techniques involving moving quantiles are introduced to generate secondary plots in which correlations and inhomogeneities in correlations are more easily detected. Several examples that illustrate the advantages of these techniques are presented and discussed.
Contact: Savageau@umich.edu
* To whom correspondence should be addressed.
TRES: comparative promoter sequence analysis
Authors: Katti Mukund V. , Sakharkar Meena K. , Ranjekar Prabhakar K. , Gupta Vidya S. 
Published: July 2002

Abstract
Summary: Comparative promoter analysis is a promising strategy for elucidation of common regulatory modules conserved in evolutionarily related sequences or in genes showing common expression profiles. To facilitate such analysis, we have developed a software tool that detects conserved transcription factor binding sites, cis-elements, palindromes and k-tuples simultaneously in a set of sequences, and thus helps to identify putative motifs for designing further experiments.
Availability: The program TRES can be accessed at URL: http://www.bic.nus.edu.sg:8888/tres
Contact: vidya@ems.ncl.res.in
*** To whom correspondance should be addressed Vidya S. Gupta, Division of Biochemical Sciences, National Chemical Laboratory, Pune-411 008, INDIA
ISYS: a decentralized, component-based approach to the

integration of heterogeneous bioinformatics resources
Authors: Siepel A. , Farmer A. , Tolopko A. , Zhuang M. , Mendes P. , Beavis W. , Sobral B. 
Published: July 2002

Abstract
Motivation: Heterogeneity of databases and software resources continues to hamper the integration of biological information. Top-down solutions are not feasible for the full-scale problem of integration across biological species and data types. Bottom-up solutions so far have not integrated, in a maximally flexible way, dynamic and interactive graphical-user-interface components with data repositories and analysis tools.
Results: We present a component-based approach that relies on a generalized platform for component integration. The platform enables independently-developed components to synchronize their behavior and exchange services, without direct knowledge of one another. An interface-based data model allows the exchange of information with minimal component interdependency. From these interactions an integrated system results, which we call ISYS\batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \(^{TM}\) \end{document}. By allowing services to be discovered dynamically based on selected objects, ISYS encourages a kind of exploratory navigation that we believe to be well-suited for applications in genomic research.
Availability: A ‘developer’s kit’ for creating software that uses the ISYS platform is available at www.ncgr.org/research/isys/devrel.html. It includes a more refined and fully documented version of the platform and a starting set of ISYS-ready components. Up-to-date descriptions of the ISYS project can be found at www.ncgr.org/research/isys.
Contact: isys@ncgr.org
* To whom correspondence should be addressed.
PrimeArray: genome-scale primer design for DNA-microarray
construction
Authors: Raddatz Günter , Dehio Michaela , Meyer Thomas F. , Dehio Christoph 
Published: July 2002

Abstract
Summary: PrimeArray is a Windows program that computes oligonuceotide primer pairs for genome-scale gene amplification by the Polymerase Chain Reaction (PCR). The program supports the automated extraction of coding sequences (CDS) from various input-file formats and allows highly automated primer pair-optimization.
Availability: The program is freely available for non-profit use via request from the authors.
Contact: christoph.dehio@unibas.ch
GeneOrder: comparing the order of genes in small genomes
Authors: Mazumder Raja , Kolaskar Ashok , Seto Donald 
Published: July 2002

Abstract
Motivation: The recent rapid rise in the availability of whole genome DNA sequence data has led to bottlenecks in their complete analysis. Specifically, there is a need for software tools that will allow mining of gene and putative gene data at a whole genome level. These new tools will complement the current set already in use for studying specific aspects of individual genes and putative genes in detail. A key software challenge is to make them user-friendly, without losing their flexibility and capability for use in research.
Results: The creation of GeneOrder—a web-based interactive, computational tool—allows researchers to compare the order of genes in two genomes. It has been tested on full genome sequence data for viruses, mitochondria and chloroplasts that were obtained from the NCBI GenBank database. It is accessible at http://www.bif.atcc.org/GENEOrder/index.html. GeneOrder prepares the comparison in table form, listing the order of similar genes. Hyperlinks are provided from this output; these lead to the ‘Protein Coding Regions’ in the NCBI database.
* To whom correspondence should be addressed.
Trev: a DNA trace editor and viewer
Authors: Bonfield James K. , Beal Kathryn F. , Betts Matthew J. , Staden Rodger 
Published: July 2002

Abstract
Trev is a DNA trace editor and viewer, which is available free for UNIX and Microsoft Windows platforms. It can read all the commonly used file formats, including the new, compact ZTR files.
Availability: ftp://ftp.mrc-lmb.cam.ac.uk/pub/staden/trev
Contact: jkb@mrc-lmb.cam.ac.uk
* To whom correspondence should be addressed.
Unsupervised technique for robust target separation and
analysis of DNA microarray spots through adaptive pixel
clustering
Authors: Bozinov Daniel , Rahnenführer Jörg 
Published: July 2002

Abstract
Motivation: Microarray images challenge existing analytical methods in many ways given that gene spots are often comprised of characteristic imperfections. Irregular contours, donut shapes, artifacts, and low or heterogeneous expression impair corresponding values for red and green intensities as well as their ratio R/G. New approaches are needed to ensure accurate data extraction from these images.
Results: Herein we introduce a novel method for intensity assessment of gene spots. The technique is based on clustering pixels of a target area into foreground and background. For this purpose we implemented two clustering algorithms derived from k-means and Partitioning Around Medoids (PAM), respectively. Results from the analysis of real gene spots indicate that our approach performs superior to other existing analytical methods. This is particularly true for spots generally considered as problematic due to imperfections or almost absent expression. Both PXPAM and PXKMEANS prove to be highly robust against various types of artifacts through adaptive partitioning, which more correctly assesses expression intensity values.
Availability: The implementation of this method is a combination of two complementary tools Extractiff (Java) and Pixclust (free statistical language R), which are available upon request from the authors.
Contact: dbozinov@unmc.edu
* To whom correspondence should be addressed.
† Both authors contributed equally to this manuscript.
The socio-economic burden of influenza
Authors: Szucs Thomas 
Published: July 2002

Abstract
Influenza epidemics and pandemics have a huge impact on society and individuals. The weight and scope of the burden of influenza varies with the age and underlying health of the patient. The disease imposes a significant burden on all individuals, but hospitalization and treatment occur more frequently in high-risk patients (the elderly and those with certain underlying medical conditions); patient populations that are increasing in size. Escalating medical costs have increased the need to quantify the burden of influenza. The first step in any such analysis is to determine the incidence of the disease; with influenza, this is often under-reported, since the illness may be confused with other viral illnesses. In addition to the direct costs of medical care, the indirect costs of influenza are substantial and stem largely from absenteeism and loss of work productivity. Estimates of the cost of influenza in the USA, France and Germany have shown that indirect costs can be five– to 10–fold higher than direct costs. Other intangible costs associated with influenza include impaired performance, which can reduce reaction times, and adverse effects on the quality of life of patients and their families. The costs of interventions should, therefore, be considered in this context. The main approach to the control of influenza and its associated costs is the administration of vaccines. Although vaccines are widely effective, the greatest potential benefits are observed within high-risk groups; vaccination is therefore recommended in many countries for high-risk patients, their carers and healthcare workers. However, the shortcomings of present vaccines, which include manufacturing limitations that prevent guaranteed adequate supply of vaccine, the difficulty in matching vaccines to circulating strains and the need for administration by injection, highlight the need for complementary treatment.
Inhibition of the VEGF receptor 2 combined with chronic hypoxia causes cell death‐dependent pulmonary endothelial cell proliferation and severe pulmonary hypertension
Authors: TARASEVICIENE‐STEWART LAIMUTE , KASAHARA YASUNORI , ALGER LORI , HIRTH PETER , MAHON GERALD MC , WALTENBERGER JOHANNES , VOELKEL NORBERT F. , TUDER RUBIN M. 
Published: July 2002

ABSTRACTOur understanding of the pathobiology of severe pulmonary hypertension, usually a fatal disease, has been hampered by the lack of information of its natural history. We have demonstrated that, in human severe pulmonary hypertension, the precapillary pulmonary arteries show occlusion by proliferated endothelial cells. Vascular endothelial growth factor (VEGF) and its receptor 2 (VEGFR‐2) are involved in proper maintenance, differentiation, and function of endothelial cells. We demonstrate here that VEGFR‐2 blockade with SU5416 in combination with chronic hypobaric hypoxia causes severe pulmonary hypertension associated with precapillary arterial occlusion by proliferating endothelial cells. Prior to and concomitant with the development of severe pulmonary hypertension, lungs of chronically hypoxic SU5416‐treated rats show significant pulmonary endothelial cell death, as demonstrated by activated caspase 3 immunostaining and TUNEL. The broad caspase inhibitor Z‐Asp‐CH2DCB prevents the development of intravascular pulmonary endothelial cell growth and severe pulmonary hypertension caused by the combination of SU5416 and chronic hypoxia.—Taraseviciene‐Stewart, L., Kasahara, Y., Alger, L., Hirth, P., McMahon, G., Waltenberger, J., Voelkel, N. F., Tuder, R. M. Inhibition of the VEGF receptor 2 combined with chronic hypoxia causes cell death‐dependent pulmonary endothelial cell proliferation and severe pulmonary hypertension. FASEB J. 15, 427‐438 (2001)
Evolution of Gene Order in the Genomes of Two Related Yeast Species
Authors: Fischer Gilles , Neuvéglise Cécile , Durrens Pascal , Gaillardin Claude , Dujon Bernard 
Published: July 2002

Changes in gene order between the genomes of two related yeast species, Saccharomyces cerevisiae and Saccharomyces bayanus var. uvarum were studied. From the dataset of a previous low coverage sequencing of the S. bayanus var.uvarum genome, 35 different synteny breakpoints between neighboring genes and two cases of local gene inversion were characterized in detail. The number and the type of the chromosomal rearrangements that have lead to these differences were identified. We show that evolution of gene order in the genomes of these two yeast species is driven mainly by gene duplication onto different chromosomes followed by differential loss of the repeated copies. In addition, local gene inversions also would result from a mechanism of gene duplication, but in an inverted orientation, followed by loss of the original copy. The identification of traces of anciently duplicated genes, called relics, show that the loss of duplicates is more frequently caused by the accumulation of numerous mutations in one of the two copies than by DNA deletion. Surprisingly, gross chromosomal rearrangements such as translocations have only a minor effect on gene order reshuffling as they account for <10% of the synteny breakpoints.[The sequence data have been submitted to the EMBL Library under accession nos. AJ316068 and AJ316069.]
Propagation of a single destabilizing mutation throughout the Escherichia coli ribonuclease HI native state
Authors: Spudich Giulietta , Lorenz Sonja , Marqusee Susan 
Published: July 2002

AbstractA point mutation (I53A) in the core of Escherichia coli RNase H* is known to destabilize both the native conformation (ΔGUN) and the kinetic intermediate (ΔGUI) by 2 kcal/mole. Here, we have used native‐state hydrogen deuterium exchange to ask how this destabilization is propagated throughout the molecule. Stability parameters were obtained for individual residues in I53A and compared with those from the wild‐type protein. A destabilization of 2 kcal/mole was observed in residues in the core but was not detected in the periphery of the molecule. These results are consistent with the localized destabilization of the core observed in the early intermediate of the kinetic folding pathway, supporting the resemblance of this kinetic intermediate to the partially unfolded form detected in the native state at equilibrium. A thermodynamic cycle also shows no interaction between Ile 53 and a residue in the periphery. There is, however, an increase in the number of denaturant‐independent exchange events in the periphery of I53A, showing that effects of the point mutation are communicated to regions outside the core, although perhaps not through changes in stability. In sum, this work shows that localized regions within a protein can be destabilized independently. Furthermore, it implies a correspondence between the kinetic intermediate and the equilibrium PUF, as the magnitude and localization of the destabilization are the same in both.
Development and Validation of a Machine Learning Model for Detection and Classification of Tertiary Lymphoid Structures in Gastrointestinal Cancers
Authors: Li Zhe , Jiang Yuming , Li Bailiang , Han Zhen , Shen Jeanne , Xia Yong , Li Ruijiang 
Published: January 2023

ImportanceTertiary lymphoid structures (TLSs) are associated with a favorable prognosis and improved response to cancer immunotherapy. The current approach for evaluation of TLSs is limited by interobserver variability and high complexity and cost of specialized imaging techniques.ObjectiveTo develop a machine learning model for automated and quantitative evaluation of TLSs based on routine histopathology images.Design, Setting, and ParticipantsIn this multicenter, international diagnostic/prognostic study, an interpretable machine learning model was developed and validated for automated detection, enumeration, and classification of TLSs in hematoxylin-eosin–stained images. A quantitative scoring system for TLSs was proposed, and its association with survival was investigated in patients with 1 of 6 types of gastrointestinal cancers. Data analysis was performed between June 2021 and March 2022.Main Outcomes and MeasuresThe diagnostic accuracy for classification of TLSs into 3 maturation states and the association of TLS score with survival were investigated.ResultsA total of 1924 patients with gastrointestinal cancer from 7 independent cohorts (median [IQR] age ranging from 57 [49-64] years to 68 [58-77] years; proportion by sex ranging from 214 of 409 patients who were male [52.3%] to 134 of 155 patients who were male [86.5%]). The machine learning model achieved high accuracies for detecting and classifying TLSs into 3 states (TLS1: 97.7%; 95% CI, 96.4%-99.0%; TLS2: 96.3%; 95% CI, 94.6%-98.0%; TLS3: 95.7%; 95% CI, 93.9%-97.5%). TLSs were detected in 62 of 155 esophageal cancers (40.0%) and up to 267 of 353 gastric cancers (75.6%). Across 6 cancer types, patients were stratified into 3 risk groups (higher and lower TLS score and no TLS) and survival outcomes compared between groups: higher vs lower TLS score (hazard ratio [HR]; 0.27; 95% CI, 0.18-0.41; P &amp;lt; .001) and lower TLS score vs no TLSs (HR, 0.65; 95% CI, 0.56-0.76; P &amp;lt; .001). TLS score remained an independent prognostic factor associated with survival after adjusting for clinicopathologic variables and tumor-infiltrating lymphocytes (eg, for colon cancer: HR, 0.11; 95% CI, 0.02-0.47; P = .003).Conclusions and RelevanceIn this study, an interpretable machine learning model was developed that may allow automated and accurate detection of TLSs on routine tissue slide. This model is complementary to the cancer staging system for risk stratification in gastrointestinal cancers.
On Nanomachines and Their Future Perspectives in Biomedicine
Authors: Ramos Docampo Miguel A. 
Published: January 2023

AbstractNano/micromotors are a class of active matter that can self‐propel converting different types of input energy into kinetic energy. The huge efforts that are made in this field over the last years result in remarkable advances. Specifically, a high number of publications have dealt with biomedical applications that these motors may offer. From the first attempts in 2D cell cultures, the research has evolved to tissue and in vivo experimentation, where motors show promising results. In this Perspective, an overview over the evolution of motors with focus on bio‐relevant environments is provided. Then, a discussion on the advances and challenges is presented, and eventually some remarks and perspectives of the field are outlined.