bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparative analysis indicates regulatory neofunctionalization of yeast duplicates
Authors: Tirosh Itay , Barkai Naama 
Published: April 2007

Abstract
Background
Gene duplication provides raw material for the generation of new functions, but most duplicates are rapidly lost due to the initial redundancy in gene function. How gene function diversifies following duplication is largely unclear. Previous studies analyzed the diversification of duplicates by characterizing their coding sequence divergence. However, functional divergence can also be attributed to changes in regulatory properties, such as protein localization or expression, which require only minor changes in gene sequence.

Results
We developed a novel method to compare expression profiles from different organisms and applied it to analyze the expression divergence of yeast duplicated genes. The expression profiles of Saccharomyces cerevisiae duplicate pairs were compared with those of their pre-duplication orthologs in Candida albicans. Duplicate pairs were classified into two classes, corresponding to symmetric versus asymmetric rates of expression divergence. The latter class includes 43 duplicate pairs in which only one copy has a significant expression similarity to the C. albicans ortholog. These may present cases of regulatory neofunctionalization, as supported also by their dispensability and variability.

Conclusion
Duplicated genes may diversify through regulatory neofunctionalization. Notably, the asymmetry of gene sequence evolution and the asymmetry of gene expression evolution are only weakly correlated, underscoring the importance of expression analysis to elucidate the evolution of novel functions.
Statistical tools for synthesizing lists of differentially expressed features in related experiments
Authors: Blangiardo Marta , Richardson Sylvia 
Published: April 2007

AbstractWe propose a novel approach for finding a list of features that are commonly perturbed in two or more experiments, quantifying the evidence of dependence between the experiments by a ratio. We present a Bayesian analysis of this ratio, which leads us to suggest two rules for choosing a cut-off on the ranked list of p values. We evaluate and compare the performance of these statistical tools in a simulation study, and show their usefulness on two real datasets.
Ancient papillomavirus-host co-speciation in Felidae
Authors: Rector Annabel , Lemey Philippe , Tachezy Ruth , Mostmans Sara , Ghim Shin-Je , Van Doorslaer Koenraad , Roelke Melody , Bush Mitchell , Montali Richard J , Joslin Janis , Burk Robert D , Jenson Alfred B , Sundberg John P , Shapiro Beth , Van Ranst Marc 
Published: April 2007

Abstract
Background
Estimating evolutionary rates for slowly evolving viruses such as papillomaviruses (PVs) is not possible using fossil calibrations directly or sequences sampled over a time-scale of decades. An ability to correlate their divergence with a host species, however, can provide a means to estimate evolutionary rates for these viruses accurately. To determine whether such an approach is feasible, we sequenced complete feline PV genomes, previously available only for the domestic cat (Felis domesticus, FdPV1), from four additional, globally distributed feline species: Lynx rufus PV type 1, Puma concolor PV type 1, Panthera leo persica PV type 1, and Uncia uncia PV type 1.

Results
The feline PVs all belong to the Lambdapapillomavirus genus, and contain an unusual second noncoding region between the early and late protein region, which is only present in members of this genus. Our maximum likelihood and Bayesian phylogenetic analyses demonstrate that the evolutionary relationships between feline PVs perfectly mirror those of their feline hosts, despite a complex and dynamic phylogeographic history. By applying host species divergence times, we provide the first precise estimates for the rate of evolution for each PV gene, with an overall evolutionary rate of 1.95 × 10-8 (95% confidence interval 1.32 × 10-8 to 2.47 × 10-8) nucleotide substitutions per site per year for the viral coding genome.

Conclusion
Our work provides evidence for long-term virus-host co-speciation of feline PVs, indicating that viral diversity in slowly evolving viruses can be used to investigate host species evolution. These findings, however, should not be extrapolated to other viral lineages without prior confirmation of virus-host co-divergence.
Global analyses of mRNA translational control during early Drosophila embryogenesis
Authors: Qin Xiaoli , Ahn Soyeon , Speed Terence P , Rubin Gerald M 
Published: April 2007

Abstract
Background
In many animals, the first few hours of life proceed with little or no transcription, and developmental regulation at these early stages is dependent on maternal cytoplasm rather than the zygotic nucleus. Translational control is critical for early Drosophila embryogenesis and is exerted mainly at the gene level. To understand post-transcriptional regulation during Drosophila early embryonic development, we used sucrose polysomal gradient analyses and GeneChip analysis to illustrate the translation profile of individual mRNAs.

Results
We determined ribosomal density and ribosomal occupancy of over 10,000 transcripts during the first ten hours after egg laying.

Conclusion
We report the extent and general nature of gene regulation at the translational level during early Drosophila embryogenesis on a genome-wide basis. The diversity of the translation profiles indicates multiple mechanisms modulating transcript-specific translation. Cluster analyses suggest that the genes involved in some biological processes are co-regulated at the translational level at certain developmental stages.
A third-generation microsatellite-based linkage map of the honey bee, Apis mellifera, and its comparison with the sequence-based physical map
Authors: Solignac Michel , Mougel Florence , Vautrin Dominique , Monnerot Monique , Cornuet Jean-Marie 
Published: April 2007

Abstract
Background:
The honey bee is a key model for social behavior and this feature led to the selection of the species for genome sequencing. A genetic map is a necessary companion to the sequence. In addition, because there was originally no physical map for the honey bee genome project, a meiotic map was the only resource for organizing the sequence assembly on the chromosomes.

Results:
We present the genetic (meiotic) map here and describe the main features that emerged from comparison with the sequence-based physical map. The genetic map of the honey bee is saturated and the chromosomes are oriented from the centromeric to the telomeric regions. The map is based on 2,008 markers and is about 40 Morgans (M) long, resulting in a marker density of one every 2.05 centiMorgans (cM). For the 186 megabases (Mb) of the genome mapped and assembled, this corresponds to a very high average recombination rate of 22.04 cM/Mb. Honey bee meiosis shows a relatively homogeneous recombination rate along and across chromosomes, as well as within and between individuals. Interference is higher than inferred from the Kosambi function of distance. In addition, numerous recombination hotspots are dispersed over the genome.

Conclusion:
The very large genetic length of the honey bee genome, its small physical size and an almost complete genome sequence with a relatively low number of genes suggest a very promising future for association mapping in the honey bee, particularly as the existence of haploid males allows easy bulk segregant analysis.
Functional dissection of the ash2 and ash1 transcriptomes provides insights into the transcriptional basis of wing phenotypes and reveals conserved protein interactions
Authors: Beltran Sergi , Angulo Mireia , Pignatelli Miguel , Serras Florenci , Corominas Montserrat 
Published: April 2007

Abstract
Background
The trithorax group (trxG) genes absent, small or homeotic discs 1 (ash1) and 2 (ash2) were isolated in a screen for mutants with abnormal imaginal discs. Mutations in either gene cause homeotic transformations but Hox genes are not their only targets. Although analysis of double mutants revealed that ash2 and ash1 mutations enhance each other's phenotypes, suggesting they are functionally related, it was shown that these proteins are subunits of distinct complexes.

Results
The analysis of wing imaginal disc transcriptomes from ash2 and ash1 mutants showed that they are highly similar. Functional annotation of regulated genes using Gene Ontology allowed identification of severely affected groups of genes that could be correlated to the wing phenotypes observed. Comparison of the differentially expressed genes with those from other genome-wide analyses revealed similarities between ASH2 and Sin3A, suggesting a putative functional relationship. Coimmunoprecipitation studies and immunolocalization on polytene chromosomes demonstrated that ASH2 and Sin3A interact with HCF (host-cell factor). The results of nucleosome western blots and clonal analysis indicated that ASH2 is necessary for trimethylation of the Lys4 on histone 3 (H3K4).

Conclusion
The similarity between the transcriptomes of ash2 and ash1 mutants supports a model in which the two genes act together to maintain stable states of transcription. Like in humans, both ASH2 and Sin3A bind HCF. Finally, the reduction of H3K4 trimethylation in ash2 mutants is the first evidence in Drosophila regarding the molecular function of this trxG gene.
Dangerous and severe personality disorder and in need of treatment
Authors: Mullen Paul E. 
Published: April 2007

SummaryThe Dangerous and Severe Personality Disorder Programme was born out of a populist law and order reaction, developed on false premises, but is now evolving into an exciting initiative for providing effective services to a group of offenders with mental illness who psychiatry, and the justice services, have so long ignored. Enthusiasm, flexibility and an evidence-based approach may yet lead to real progress towards the improved management of disturbed high-risk offenders, improving the psychological and social functioning of the offenders as well as delivering a safer community.
Dangerous and severe personality disorder: antecedents and origins
Authors: Maden Anthony 
Published: April 2007

SummaryThe origins of the Dangerous and Severe Pesonality Disorder (DSPD) Programme can be traced to developments in structured assessment and services for the cognitive–behavioural treatment of sexual and violent offenders in other countries. A comparison with these other services highlights the strengths and weaknesses of DSPD. The decision to use a medical model raises ethical and financial questions that may jeopardise the Programme's future.
Zuclopenthixol in adults with intellectual disabilities and aggressive behaviours
Authors: Haessler Frank , Glaser Thomas , Beneke Manfred , Pap Akos F. , Bodenschatz Ralf , Reis Olaf 
Published: April 2007

SummaryWe investigated the effects of zuclopenthixol on aggressive behaviour in patients with intellectual disabilities by randomly withdrawing it after a 6-week period of open treatment. Of the 49 patients responding to the treatment, 39 took part in a randomised withdrawal trial. The placebo subgroup (n=20) showed more aggressive behaviour as indicated by outcomes observed by external raters on the Modified Overt Aggression Scale than did the continuing subgroup (n=19). The results indicate that discontinuation of zuclopenthixol in this population leads to an increase in aggressive behaviour.
All-cause mortality among recipients of electroconvulsive therapy
Authors: Munk-Olsen Trine , Laursen Thomas Munk , Videbech Poul , Mortensen Preben Bo , Rosenberg Raben 
Published: April 2007

BackgroundStudies investigating mortality secondary to electroconvulsive therapy (ECT) are few.AimsTo assess the risk of mortality from natural and unnatural causes among ECT recipients compared with other psychiatric in-patients over a 25-year period.MethodRegister-based cohort study of all in-patients admitted to a psychiatric hospital from 1976 to 2000. Cause-specific mortality was analysed using log–linear Poisson regression.ResultsThere were 783 deceased in-patients who had received ECT compared with 5781 who had not. Patients who had received ECT had a lower overall mortality rate from natural causes (RR=0.82,95% CI 0.74–0.90) but a slightly higher suicide rate (RR=1.20,95% CI 0.99–1.47), especially within the first 7 days after the last ECT treatment (RR=4.82,95% CI 2.12–10.95).ConclusionsFurther investigation of the effect of ECT on physical health and the observed increased suicide rate immediately following treatment are needed, although the last finding is likely to result from selection bias.
Serotonergic function in children with attention-deficit hyperactivity disorder
Authors: Flory Janine D. , Newcorn Jeffrey H. , Miller Carlin , Harty Seth , Halperin Jeffrey M. 
Published: April 2007

BackgroundImpulsive aggression in adulthood is associated with disturbances in serotonergic function. In contrast, research examining this association in childhood has yielded inconsistent results.AimsThe current study examined the prospective relationship between serotonergic function measured in childhood and the later emergence of antisocial personality disorder.MethodHormonal response to fenfluramine, an index of serotonergic function, was assessed in 58 children with attention-deficit hyperactivity disorder between 1990 and 1997 when they were aged 7–11 years. Approximately 9 years later these individuals were evaluated for antisocial personality disorder.ResultsLower serotonergic responsivity assessed in childhood predicted the development of antisocial personality disorder (t (56)=2.25, P=0.028).ConclusionsThese results provide a critical link between the child and adult literature on the covariation of impulsive aggression and serotonergic function and suggest a potential explanation for inconsistencies in the childhood literature.
Safety of selective serotonin reuptake inhibitors in pregnancy
Authors: Donnelly Allison , Paton Carol 
Published: April 2007

Aims and MethodSelective serotonin reuptake inhibitors (SSRIs) are recommended by the National Institute for Clinical Excellence as first-line drugs for the treatment of depression, but there is emerging evidence that they might not be entirely safe in pregnancy. We reviewed the literature in this area.ResultsSome data indicate an association between first-trimester SSRI exposure, particularly with paroxetine, and an increased risk of some major congenital malformations. Stronger evidence supports an association with small reductions in gestational age and neonatal withdrawal symptoms.Clinical ImplicationsRisks and benefits of using SSRIs during pregnancy should be discussed with the patient, and a joint decision made between prescriber and patient regarding treatment. Limited data suggest that other SSRIs are safer than paroxetine in pregnancy.
Phase I and Correlative Biology Study of Cilengitide in Patients With Recurrent Malignant Glioma
Authors: Nabors L. Burt , Mikkelsen Tom , Rosenfeld Steven S. , Hochberg Fred , Akella Narasimha S. , Fisher Joy D. , Cloud Gretchen A. , Zhang Yu , Carson Kathryn , Wittemer Sabine M. , Colevas A. Dimitrios , Grossman Stuart A. 
Published: April 2007

Purpose This multi-institutional phase I trial was designed to determine the maximum-tolerated dose (MTD) of cilengitide (EMD 121974) and to evaluate the use of perfusion magnetic resonance imaging (MRI) in patients with recurrent malignant glioma. Patients and Methods Patients received cilengitide twice weekly on a continuous basis. A treatment cycle was defined as 4 weeks. Treatment-related dose-limiting toxicity (DLT) was defined as any grade 3 or 4 nonhematologic toxicity or grade 4 hematologic toxicity of any duration. Results A total of 51 patients were enrolled in cohorts of six patients to doses of 120, 240, 360, 480, 600, 1,200, 1,800, and 2,400 mg/m2 administered as a twice weekly intravenous infusion. Three patients progressed early and were inevaluable for toxicity assessment. The DLTs observed were one thrombosis (120 mg/m2), one grade 4 joint and bone pain (480 mg/m2), one thrombocytopenia (600 mg/m2) and one anorexia, hypoglycemia, and hyponatremia (800 mg/m2). The MTD was not reached. Two patients demonstrated complete response, three patients had partial response, and four patients had stable disease. Perfusion MRI revealed a significant relationship between the change in tumor relative cerebral blood flow (rCBF) from baseline and area under the plasma concentration versus time curve after 16 weeks of therapy. Conclusion Cilengitide is well tolerated to doses of 2,400 mg/m2, durable complete and partial responses were seen in this phase I study, and clinical response appears related to rCBF changes.
Sex Differences in Lung Cancer Survival: Do Tumors Behave Differently in Elderly Women?
Authors: Wisnivesky Juan P. , Halm Ethan A. 
Published: April 2007

Purpose Women with lung cancer appear to have better survival. Whether this results from better response to treatment, different tumor biology, or a longer life expectancy is not well understood. This study sought to assess sex differences in the natural history of lung cancer after controlling for unrelated causes of death and type of treatment. Methods This study included 18,967 elderly patients with stage I and II non–small-cell lung cancer diagnosed between 1991 and 1999 from the Surveillance, Epidemiology, and End Results registry linked to Medicare records. Patients were grouped into three categories according to the treatment received: surgery, radiation or chemotherapy but no surgery, and untreated cases. We used stratified and multivariate analyses to evaluate sex differences in survival using three methods to control for competing risks: lung cancer–specific survival, overall survival adjusting for comorbidities, and relative survival. Sensitivity analysis was used to test whether potential differences in smoking could account for the observed association of sex with survival. Results Women in all treatment groups had better lung cancer–specific, overall, and relative survival than did men (P < .0001). Stratified and multivariate analyses showed that women had better survival than did men after controlling for confounders. Sensitivity analyses showed that potential sex differences in smoking did not explain our findings. Conclusion In this national, population-based sample, elderly women with early lung cancer had better risk-adjusted survival regardless of the type of treatment. That sex differences were observed among untreated patients suggests that lung cancer in women may have a different natural history.
Suffering With Advanced Cancer
Authors: Wilson Keith G. , Chochinov Harvey Max , McPherson Christine J. , LeMay Katerine , Allard Pierre , Chary Srini , Gagnon Pierre R. , Macmillan Karen , De Luca Marina , O'Shea Fiona , Kuhl David , Fainsinger Robin L. 
Published: April 2007

Purpose The alleviation of suffering is a central goal of palliative care, but little research has addressed the construct of suffering as a global experience of the whole person. We inquired into the sense of suffering among patients with advanced cancer to investigate its causes and correlates. Patients and Methods Semistructured interviews were administered to 381 patients. The interviews inquired about physical symptoms, social concerns, psychological problems, and existential issues. We also asked, “In an overall, general sense, do you feel that you are suffering?” Results Almost half (49.3%) of respondents did not consider themselves to be suffering, and 24.9% felt that they suffered only mildly. However, 98 participants (25.7%) were suffering at a moderate-to-extreme level. The latter participants were more likely to experience significant distress on 20 of the 21 items addressing symptoms and concerns; the highest correlations were with general malaise (rho [ρ]= 0.56), weakness (ρ = 0.42), pain (ρ = 0.40), and depression (ρ = .39). In regression analyses, physical symptoms, psychological distress, and existential concerns, but not social issues, contributed to the prediction of suffering. In qualitative narratives, physical problems accounted for approximately half (49.5%) of patient reports of suffering, with psychological, existential, and social concerns accounting for 14.0%, 17.7%, and 18.8%, respectively. Conclusion Many patients with advanced cancer do not consider themselves to be suffering. For those who do, suffering is a multidimensional experience related most strongly to physical symptoms, but with contributions from psychological distress, existential concerns, and social-relational worries.
Phase II Trial of Bevacizumab and Erlotinib in Carcinomas of Unknown Primary Site: The Minnie Pearl Cancer Research Network
Authors: Hainsworth John D. , Spigel David R. , Farley Cindy , Thompson Dana S. , Shipley Dianna L. , Greco F. Anthony 
Published: April 2007

Purpose Treatment remains poor for many patients with carcinoma of unknown primary site (CUP), and no effective second-line treatment has been identified. Combination inhibition of vascular endothelial growth factor (VEGF) and the epidermal growth factor receptor (EGFR) with bevacizumab and erlotinib has proved efficacious and well tolerated in other solid tumors. We therefore have evaluated the efficacy and toxicity of this combination in patients with CUP. Patients and Methods Patients with CUP who either had received previous chemotherapy or were previously untreated with poor-prognosis clinical features were eligible for this study. All patients received bevacizumab 10 mg/kg IV every 2 weeks, along with erlotinib 150 mg orally daily. Patients were re-evaluated after 8 weeks of treatment; those with objective response or stable disease continued treatment until disease progression. Results Forty-seven (92%) of 51 patients received at least 8 weeks of treatment. Five patients (10%) had partial responses, and 29 patients (61%) had stable disease as the best response. The median survival for the entire group was 7.4 months, with 33% of patients alive at 1 year. This regimen was well tolerated by most patients. Conclusion The combination of bevacizumab and erlotinib has substantial activity in the treatment of patients with CUP. The median survival is superior to survival previously reported with second-line chemotherapy, and is similar to the results of many first-line chemotherapy trials in this setting. This regimen merits further evaluation in patients with CUP.
Numerical Analysis of the Flatness of Thin, Rolled Steel Strip on the Runout Table
Authors: Zhou Zhongqing , Lam YeeCheong , Thomson P F , Yuen D D W 
Published: April 2007

A finite element analysis of the flatness of thin, rolled steel strip is presented. The occurrence of edge-wave and centre-buckle is predicted numerically by solving the eigenvalue problem. The form of buckles is calculated using a non-linear load-displacement analysis. Buckling changes from the centre to the edge as the maximum difference in temperature between the edge and centre increases; correspondingly, the amplitude increases and the wavelength decreases. Because uniform applied tension then decreases the compressive stress at the edge and increases the stress in the centre, a centre-buckled strip is flattened by applied tension, but edge-buckling becomes more severe and applied tension may change the type of buckling from the centre to the edge. Crowned strip resists buckling whereas a concave profile tends to promote it. The effects of the magnitude of the crown or concavity on centre-buckling of the strip are more significant than on edge-buckling.