bluuebunny/crossref_metadata_2025_split huggingface dataset:
Classification and risk stratification of invasive breast carcinomas using a real-time quantitative RT-PCR assay
Authors: Perreard Laurent , Fan Cheng , Quackenbush John F , Mullins Michael , Gauthier Nicholas P , Nelson Edward , Mone Mary , Hansen Heidi , Buys Saundra S , Rasmussen Karen , Orrico Alejandra Ruiz , Dreher Donna , Walters Rhonda , Parker Joel , Hu Zhiyuan , He Xiaping , Palazzo Juan P , Olopade Olufunmilayo I , Szabo Aniko , Perou Charles M , Bernard Philip S 
Published: April 2006

Abstract
Introduction
Predicting the clinical course of breast cancer is often difficult because it is a diverse disease comprised of many biological subtypes. Gene expression profiling by microarray analysis has identified breast cancer signatures that are important for prognosis and treatment. In the current article, we use microarray analysis and a real-time quantitative reverse-transcription (qRT)-PCR assay to risk-stratify breast cancers based on biological 'intrinsic' subtypes and proliferation.

Methods
Gene sets were selected from microarray data to assess proliferation and to classify breast cancers into four different molecular subtypes, designated Luminal, Normal-like, HER2+/ER-, and Basal-like. One-hundred and twenty-three breast samples (117 invasive carcinomas, one fibroadenoma and five normal tissues) and three breast cancer cell lines were prospectively analyzed using a microarray (Agilent) and a qRT-PCR assay comprised of 53 genes. Biological subtypes were assigned from the microarray and qRT-PCR data by hierarchical clustering. A proliferation signature was used as a single meta-gene (log2 average of 14 genes) to predict outcome within the context of estrogen receptor status and biological 'intrinsic' subtype.

Results
We found that the qRT-PCR assay could determine the intrinsic subtype (93% concordance with microarray-based assignments) and that the intrinsic subtypes were predictive of outcome. The proliferation meta-gene provided additional prognostic information for patients with the Luminal subtype (P = 0.0012), and for patients with estrogen receptor-positive tumors (P = 3.4 × 10-6). High proliferation in the Luminal subtype conferred a 19-fold relative risk of relapse (confidence interval = 95%) compared with Luminal tumors with low proliferation.

Conclusion
A real-time qRT-PCR assay can recapitulate microarray classifications of breast cancer and can risk-stratify patients using the intrinsic subtype and proliferation. The proliferation meta-gene offers an objective and quantitative measurement for grade and adds significant prognostic information to the biological subtypes.
Plasma DNA concentration as a predictor of mortality and sepsis in critically ill patients
Authors: Rhodes Andrew , Wort Stephen J , Thomas Helen , Collinson Paul , Bennett E David 
Published: April 2006

Abstract
Introduction
Risk stratification of severely ill patients remains problematic, resulting in increased interest in potential circulating markers, such as cytokines, procalcitonin and brain natriuretic peptide. Recent reports have indicated the usefulness of plasma DNA as a prognostic marker in various disease states such as trauma, myocardial infarction and stroke. The present study assesses the significance of raised levels of plasma DNA on admission to the intensive care unit (ICU) in terms of its ability to predict disease severity or prognosis.

Methods
Fifty-two consecutive patients were studied in a general ICU. Blood samples were taken on admission and were stored for further analysis. Plasma DNA levels were estimated by a PCR method using primers for the human β-haemoglobin gene.

Results
Sixteen of the 52 patients investigated died within 3 months of sampling. Nineteen of the 52 patients developed either severe sepsis or septic shock. Plasma DNA was higher in ICU patients than in healthy controls and was also higher in patients who developed sepsis (192 (65–362) ng/ml versus 74 (46–156) ng/ml, P = 0.03) or who subsequently died either in the ICU (321 (185–430) ng/ml versus 71 (46–113) ng/ml, P < 0.001) or in hospital (260 (151–380) ng/ml versus 68 (47–103) ng/ml, P < 0.001). Plasma DNA concentrations were found to be significantly higher in patients who died in the ICU. Multiple logistic regression analysis determined plasma DNA to be an independent predictor of mortality (odds ratio, 1.002 (95% confidence interval, 1.0–1.004), P = 0.05). Plasma DNA had a sensitivity of 92% and a specificity of 80% when a concentration higher than 127 ng/ml was taken as a predictor for death on the ICU.

Conclusion
Plasma DNA may be a useful prognostic marker of mortality and sepsis in intensive care patients.
Benchmarking ortholog identification methods using functional genomics data
Authors: Hulsen Tim , Huynen Martijn A , de Vlieg Jacob , Groenen Peter MA 
Published: April 2006

Abstract
Background
The transfer of functional annotations from model organism proteins to human proteins is one of the main applications of comparative genomics. Various methods are used to analyze cross-species orthologous relationships according to an operational definition of orthology. Often the definition of orthology is incorrectly interpreted as a prediction of proteins that are functionally equivalent across species, while in fact it only defines the existence of a common ancestor for a gene in different species. However, it has been demonstrated that orthologs often reveal significant functional similarity. Therefore, the quality of the orthology prediction is an important factor in the transfer of functional annotations (and other related information). To identify protein pairs with the highest possible functional similarity, it is important to qualify ortholog identification methods.

Results
To measure the similarity in function of proteins from different species we used functional genomics data, such as expression data and protein interaction data. We tested several of the most popular ortholog identification methods. In general, we observed a sensitivity/selectivity trade-off: the functional similarity scores per orthologous pair of sequences become higher when the number of proteins included in the ortholog groups decreases.

Conclusion
By combining the sensitivity and the selectivity into an overall score, we show that the InParanoid program is the best ortholog identification method in terms of identifying functionally equivalent proteins.
APTIMA PCA3 Molecular Urine Test: Development of a Method to Aid in the Diagnosis of Prostate Cancer
Authors: Groskopf Jack , Aubin Sheila MJ , Deras Ina Lim , Blase Amy , Bodrug Sharon , Clark Craig , Brentano Steven , Mathis Jeannette , Pham Jimmykim , Meyer Troels , Cass Michelle , Hodge Petrea , Macairan Maria Luz , Marks Leonard S , Rittenhouse Harry 
Published: April 2006

Abstract
Background: Prostate cancer gene 3 (PCA3) encodes a prostate-specific mRNA that has shown promise as a prostate cancer diagnostic tool. This report describes the characterization of a prototype quantitative PCA3-based test for whole urine.
Methods: Whole-urine specimens were collected after digital rectal examination from 3 groups: men scheduled for prostate biopsy (n = 70), healthy men (&lt;45 years of age with no known prostate cancer risk factors; n = 52), and men who had undergone radical prostatectomy (n = 21). PCA3 and prostate-specific antigen (PSA) mRNAs were isolated, amplified, and quantified by use of Gen-Probe DTS400® Systems. Prostate biopsy results were correlated with the PCA3/PSA mRNA ratio, and PSA mRNA concentrations were used to normalize PCA3 signals and confirm the yield of prostate-specific RNA. Assay precision, specimen stability, and mRNA yield were also evaluated.
Results: The specimen informative rate (fraction of specimens yielding sufficient RNA for analysis) was 98.2%. In this clinical research study, ROC curve analysis of prebiopsy specimens yielded an area under the curve of 0.746; sensitivity was 69% and specificity 79%. Serum PSA assay specificity was 28% for this same group. PCA3 and PSA mRNAs were undetectable in postprostatectomy specimens except for one man with recurrent prostate cancer. Assay interrun CVs were ≤12%. Both mRNAs were stable in processed urine up to 5 days at 4 °C and after 5 freeze–thaw cycles.
Conclusion: The APTIMA® PCA3 assay combines simple specimen processing with precise assays and existing instruments and could add specificity to the current algorithm for prostate cancer diagnosis.
Ultrasensitive Monitoring of HIV-1 Viral Load by a Low-Cost Real-Time Reverse Transcription-PCR Assay with Internal Control for the 5′ Long Terminal Repeat Domain
Authors: Drosten Christian , Panning Marcus , Drexler Jan Felix , Hänsel Florian , Pedroso Celia , Yeats Jane , de Souza Luna Luciano Kleber , Samuel Matthew , Liedigk Britta , Lippert Ute , Stürmer Martin , Doerr Hans Wilhelm , Brites Carlos , Preiser Wolfgang 
Published: April 2006

Abstract
Background: Current HIV-1 viral-load assays are too expensive for resource-limited settings. In some countries, monitoring of antiretroviral therapy is now more expensive than treatment itself. In addition, some commercial assays have shown shortcomings in quantifying rare genotypes.
Methods: We evaluated real-time reverse transcription-PCR with internal control targeting the conserved long terminal repeat (LTR) domain of HIV-1 on reference panels and patient samples from Brazil (n = 1186), South Africa (n = 130), India (n = 44), and Germany (n = 127).
Results: The detection limit was 31.9 IU of HIV-1 RNA/mL of plasma (&gt;95% probability of detection, Probit analysis). The internal control showed inhibition in 3.7% of samples (95% confidence interval, 2.32%–5.9%; n = 454; 40 different runs). Comparative qualitative testing yielded the following: Roche Amplicor vs LTR assay (n = 431 samples), 51.7% vs 65% positives; Amplicor Ultrasensitive vs LTR (n = 133), 81.2% vs 82.7%; BioMerieux NucliSens HIV-1 QT (n = 453), 60.5% vs 65.1%; Bayer Versant 3.0 (n = 433), 57.7% vs 55.4%; total (n = 1450), 59.0% vs 63.8% positives. Intra-/interassay variability at medium and near-negative concentrations was 18%–51%. The quantification range was 50–10 000 000 IU/mL. Viral loads for subtypes A–D, F–J, AE, and AG yielded mean differences of 0.31 log10 compared with Amplicor in the 103–104 IU/mL range. HIV-1 N and O were not detected by Amplicor, but yielded up to 180 180.00 IU/mL in the LTR assay. Viral loads in stored samples from all countries, compared with Amplicor, NucliSens, or Versant, yielded regression line slopes (SD) of 0.9 (0.13) (P &lt;0.001 for all).
Conclusions: This method offers all features of commercial assays and covers all relevant genotypes. It could allow general monitoring of antiretroviral therapy in resource-limited settings.
Segregating Variation in the Transcriptome:CisRegulation and Additivity of Effects
Authors: Hughes Kimberly A , Ayroles Julien F , Reedy Melissa M , Drnevich Jenny M , Rowe Kevin C , Ruedi Elizabeth A , Cáceres Carla E , Paige Ken N 
Published: April 2006

AbstractProperties of genes underlying variation in complex traits are largely unknown, especially for variation that segregates within populations. Here, we evaluate allelic effects, cis and trans regulation, and dominance patterns of transcripts that are genetically variable in a natural population of Drosophila melanogaster. Our results indicate that genetic variation due to the third chromosome causes mainly additive and nearly additive effects on gene expression, that cis and trans effects on gene expression are numerically about equal, and that cis effects account for more genetic variation than do trans effects. We also evaluated patterns of variation in different functional categories and determined that genes involved in metabolic processes are overrepresented among variable transcripts, but those involved in development, transcription regulation, and signal transduction are underrepresented. However, transcripts for proteins known to be involved in protein–protein interactions are proportionally represented among variable transcripts.
A Genetic Test of the Role of the Maternal Pronucleus in Wolbachia-Induced Cytoplasmic Incompatibility in Drosophila melanogaster
Authors: Ferree Patrick M , Sullivan William 
Published: April 2006

Abstract
Cytoplasmic incompatibility (CI) is a reproductive sterility found in arthropods that is caused by the endoparasitic bacteria Wolbachia. In CI, host progeny fail to develop during early embryogenesis if Wolbachia-infected males fertilize uninfected females. It is widely accepted that this lethality is caused by some unknown Wolbachia-induced modification of the paternal nuclear material in the host testes. However, the direct means by which this modification leads to early embryonic death are currently unresolved. Results from previous studies suggested that CI lethality occurs as a result of asynchrony in cell cycle timing between the paternal and maternal pronuclei. This hypothesis can be tested experimentally by the prediction that the Wolbachia-modified paternal pronucleus should support androgenetic development (i.e., from the paternal pronucleus only). Using specific mutations in Drosophila melanogaster that produce androgenetic progeny, we demonstrate that the Wolbachia-induced modification inhibits this type of development. This result suggests that CI occurs independently of the maternal pronucleus and argues against pronuclear asynchrony as the primary cause of CI lethality. We propose that CI occurs instead as the result of either a developmentally incompetent paternal pronucleus or asynchrony between the paternal pronucleus and the cell cycle of the egg cytoplasm.
Mapping Novel Traits by Array-Assisted Bulk Segregant Analysis in Saccharomyces cerevisiae
Authors: Brauer Matthew J , Christianson Cheryl M , Pai Dave A , Dunham Maitreya J 
Published: April 2006

Abstract
We demonstrate a new method, microarray-assisted bulk segregant analysis, for mapping traits in yeast by genotyping pooled segregants. We apply a probabilistic model to the progeny of a single cross and as little as two microarray hybridizations to reliably map an auxotrophic marker, a Mendelian trait, and a major-effect quantitative trait locus.
The Ladies in Skelton's 'Garland, of Laurel'
Authors: Tucker M. J. 
Published: April 2006

The mystery of John Skelton's Howard connection has never been satisfactorily explained. Indeed, one usually thinks of the Tudor poet (1460?-1529) as a court poet and tutor to Henry VIII rather than as the protégé of the Howard Countess of Surrey who directed her daughters and gentlewomen to honor him with a laurel crown. Of course, the recitation of this apparently biographical incident in which eleven gentlewomen joyfully decked Skelton's brow with laurel, became the basis for Skelton's most autobiographical poem, The Garland of Laurel.Published October 3, 1523, the usual assumption is that the Countess of Surrey is none other than Elizabeth Howard, née Stafford (d. 1558), the wife of Thomas Howard, Earl of Surrey and in due course third Duke of Norfolk (d. 1554).
The Bibliotheca of Gabriel Harvey
Authors: Stern Virginia F. 
Published: April 2006

The titles in an individual's library should be an excellent indicator of his interests. In the case of the extensive and remarkably varied collection of annotated volumes belonging to the Renaissance scholar Gabriel Harvey, knowledge of the contents of his library can reveal much not only about the man but about his era as well.Harvey, eldest of a family of four brothers and two sisters, was born about 1550 in Essex at Saffron Walden, an important town of that period, situated about fifteen miles southeast of Cambridge. A person of considerable intellectual attainments he became a Cambridge don and by 1578 had published several original works in Latin prose and poetry. Although highly esteemed by his close friend the poet Edmund Spenser and by a number of eminent Cambridge scholars, Harvey was undoubtedly resented by others, perhaps because of his espousal of such antitraditional notions as Ramus’ reforms of Aristotelian logic, his awareness of his own intellectual superiority, and his fellow students' disdain for his middle-class background.
St. Thomas More and Music: The Epigrams
Authors: Carpenter Nan C. 
Published: April 2006

Among the Latin epigrams of Thomas More, several are highly interesting for musical reasons. Two bear the caption ‘Poem Translated from an English Song.’ The first of these (63), beginning ‘O cor triste,’ reads in literal English translation,Break, sad heart, pitiably engulfed in deepest woe. Let this be the end of your punishment. Show your mistress your bloody wounds. In short, it is she, only she, who will keep us two apart. Alas, how long shall I in my misery thus weep and complain? Come, dreaded death, and release me from monstrous woes.The song on which this is based has apparently not yet been found.
Renaissance Attitudes to New Testament Apocryphal Writings: Jacques Lèfevre d'Étaples and His Epigones
Authors: Backus Irena 
Published: April 2006

AbstractThe standard medieval view of New Testament Apocrypha was that they were Christian writings (related to matters treated in the canonical books of the Bible), which had to be treated with caution and often dismissed as heretical. A list of the Apocrypha figured in the [Pseudo-]Gelasian Decree. In the Renaissance, for authors such as Lèfevre d'Etaples, Nicholas Gerbel and many others, the term assumed a multiplicity of meanings, both positive and negative. This article shows that although no attempts were made in the early 16th century to bring N. T. Apocrypha together into a corpus, the editors' ambivalent and complex attitude to texts such as the Laodiceans or Paul's Correspondence with Seneca led to their definitive marginalisation and encouraged their subsequent publication (by Fabricius and others) as corpora of dubious writings.
Donor cell leukemia in a patient developing 11 months after an allogeneic bone marrow transplantation for chronic myeloid leukemia
Authors: Ataergin Selmin , Arpaci Fikret , Cetin Turker , Guran Sefik , Yakicier Cengiz , Beyzadeoglu Murat , Ozet Ahmet 
Published: April 2006

AbstractA 38‐year‐old female with chronic myeloid leukemia underwent an allogeneic bone marrow transplantation from her full‐matched brother. Eleven months later, she readmitted with an acute leukemia that was shown to be of donor origin. The patient never achieved a remission even after chemotherapies with cytarabine and mitoxantrone, donor lymphocyte infusion, and second allogeneic peripheral blood stem cell transplantation. Donor cell leukemia (DCL) is sometimes misdiagnosed as relapse by clinicians and the real incidence may be higher than expected. Cytogenetic and molecular techniques may be helpful to clarify the issue of the leukemia. The current case is another case of DCL reported in the literature after an allogeneic transplant for a kind of leukemia. Am. J. Hematol. 81:370–373, 2006
Modeling of Cdc25B Dual Specifity Protein Phosphatase Inhibitors: Docking of Ligands and Enzymatic Inhibition Mechanism
Authors: Lavecchia Antonio , Cosconati Sandro , Limongelli Vittorio , Novellino Ettore 
Published: April 2006

AbstractThe Cdc25 dual specificity phosphatases have central roles in coordinating cellular signalling processes and cell proliferation. It has been reported that an improper amplification or activation of these enzymes is a distinctive feature of a number of human cancers, including breast cancers. Thus, the inhibition of Cdc25 phosphatases might provide a novel approach for the discovery of new and selective antitumor agents. By using the crystal structure of the catalytic domain of Cdc25B, structural models for the interaction of various Cdc25B inhibitors (1–13) with the enzyme were generated by computational docking. The parallel use of two efficient and predictive docking programs, AutoDock and GOLD, allowed mutual validation of the predicted binding poses. To evaluate their quality, the models were validated with known structure–activity relationships and site‐directed mutagenesis data. The results provide an improved basis for structure‐based ligand design and suggest a possible explanation for the inhibition mechanism of the examined Cdc25B ligands. We suggest that the recurring motif of a tight interaction between the inhibitor and the two arginine residues, 482 and 544, is of prime importance for reversible enzyme inhibition. In contrast, the irreversible inhibition mechanism of 1–4 seems to be associated with the close vicinity of the quinone ring and the Cys473 catalytic thiolate. We believe that this extensive study might provide useful hints to guide the development of new potent Cdc25B inhibitors as novel anticancer drugs.
A Fluorine Scan at the Catalytic Center of Thrombin: CF, COH, and COMe Bioisosterism and Fluorine Effects on pKaand log DValues
Authors: Schweizer Eliane , Hoffmann‐Röder Anja , Schärer Kaspar , Olsen Jacob A. , Fäh Christoph , Seiler Paul , Obst‐Sander Ulrike , Wagner Björn , Kansy Manfred , Diederich François 
Published: April 2006

AbstractA series of 16 tricyclic thrombin inhibitors was prepared by using the 1,3‐dipolar cycloaddition of azomethine ylides derived from 3‐ or 4‐hydroxyproline and 4‐bromobenzaldehyde, withN‐(4‐fluorobenzyl)maleimide as the key step. The terminal pyrrolidine ring of the inhibitors was systematically substituted to explore the potential bioisosteric behavior of CF, COH, and COMe residues pointing into the environment of the catalytic center of a serine protease. X‐ray crystal structure analyses revealed a distinct puckering preference of this ring. Substitution by F, HO, and MeO has a strong effect on the basicity of the adjacent pyrrolidine nitrogen center which originates from two σ‐inductive pathways between this center and the electronegative O and F atoms.gem‐Difluorination decreases the pKavalue of this tertiary amine center to <2, making the conjugated ammonium ion a moderately strong acid. Unexpectedly, F substitution next to the nitrogen center reduced the lipophilicity of the ligands, as revealed by measurements of the logarithmic partition coefficient log D. The biological assays showed that all compounds are thrombin inhibitors with activities betweenKi=0.08 and 2.17 μM. Bioisosteric behavior of F, HO, and MeO substituents was observed. Their electronegative F and O atoms undergo energetically similar polar interactions with positively polarized centers, such as the N atom of His 57 which is hydrogen bonded to the catalytic Ser 195. However, for energetically similar polar interactions of CF, COH, and COMe to occur, sufficient space is necessary for the accommodation of the Me group of the COMe residue, and a H‐bond acceptor must be present to prevent unfavorable desolvation of the COH residue.
A microphone array system with echo canceller
Authors: Kobayashi Kazunori , Furuya Ken'Ichi , Kataoka Akitoshi 
Published: April 2006

AbstractThis paper proposes a microphone array unified with an echo canceller that resolves the problem of deteriorated echo suppression performance due to variations of the echo path when a microphone array and an echo canceller are connected. In a teleconferencing system, high‐quality sound acquisition with noise suppression is desirable in addition to acoustic echo suppression. However, in a configuration in which a microphone array to suppress the noise and an echo canceller to suppress the echo are simply connected, the adaptation for the echo canceller cannot follow the echo path variations due to directivity control of the microphone array, so that there is a problem of deteriorated echo suppression performance. In the microphone array with an echo canceller proposed in this paper, the training of the microphone array and that of the echo canceller are performed in a unified way. In this way, the problem of deteriorated echo suppression performance due to echo path variations can be resolved. An evaluation experiment shows that the proposed method can perform stable noise suppression and echo cancellation. © 2006 Wiley Periodicals, Inc. Electron Comm Jpn Pt 3, 89(10): 23–32, 2006; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/ecjc.20090