bluuebunny/crossref_metadata_2025_split huggingface dataset:
Protein splicing In Cis and In Trans
Authors: Saleh Lana , Perler Francine B. 
Published: August 2006

AbstractIntein‐mediated protein splicing is a self‐catalytic process in which the intervening intein sequence is removed from a precursor protein and the flanking extein segments are ligated with a native peptide bond. Splice junction proximal residues and internal residues within the intein direct these reactions. The identity of these residues varies in each intein, as groups of related residues populate conserved motifs. Although the basics of the four‐step protein splicing pathway are known, mechanistic details are still unknown. Structural and kinetic analyses are beginning to shed some light. Several structures were reported for precursor proteins with mutations in catalytic residues, which stabilize the precursors for crystallographic study. Progress is being made despite limitations inherent in using mutated precursors. However, no uniform mechanism has emerged. Kinetic parameters were determined using conditional trans‐splicing (splicing of split precursor fragments after intein reassembly). Several groups concluded that the rate of the initial acyl rearrangement step is rapid and Asn cyclization (step 3) is slow, suggesting that this latter step is rate limiting. Understanding the protein splicing pathway has allowed scientists to harness inteins for numerous applications. © 2006 The Japan Chemical Journal Forum and Wiley Periodicals, Inc. Chem Rec 6: 183–193; 2006: Published online in Wiley InterScience (www.interscience.wiley.com) DOI 10.1002/tcr.20082
Structure and function of cis‐prenyl chain elongating enzymes
Authors: Takahashi Seiji , Koyama Tanetoshi 
Published: August 2006

AbstractAll carbon skeletons of isoprenoids, whose chain lengths vary widely from geranyl diphosphate (C10) to natural rubber (C>10,000), are synthesized by sequential condensation of isopentenyl diphosphate with an allylic diphosphate through catalytic functions of a group of enzymes commonly called “prenyltransferases.” Prenyltransferases are classified into two major groups, trans‐ or (E)‐prenyltransferases and cis‐ or (Z)‐prenyltransferases, according to the geometry of the prenyl chain units in the products. From the year 1987, many genes encoding trans‐prenyltransferases were cloned and clearly characterized. In contrast, the structure and detailed mechanism of cis‐prenyltransferase was completely unknown until the identification of a gene encoding the undecaprenyl diphosphate (UPP) synthase from Micrococcus luteus B‐P 26 in 1998. Not only the primary but also the tertiary structure of the UPP synthase is quite different from that of the trans‐prenyltransferases. Multiple alignment of the primary structures of cis‐prenyltransferases identified from various organisms reveals five highly conserved regions. Site‐directed mutagenesis of the conserved amino acid residues in UPP synthases based on the crystal structure has elucidated the basic catalytic mechanisms. Moreover, comparison of the structures of short‐, medium‐, and long‐chain cis‐prenyltransferases reveals important amino acid residues for product chain length determination, which enabled us to understand the regulation mechanism of the ultimate chain length among cis‐prenyltransferases. © 2006 The Japan Chemical Journal Forum and Wiley Periodicals, Inc. Chem Rec 6: 194–205; 2006: Published online in Wiley InterScience (www.interscience.wiley.com) DOI 10.1002/tcr.20083
Total syntheses of polyketide‐derived bioactive natural products
Authors: Tatsuta Kuniaki , Hosokawa Seijiro 
Published: August 2006

AbstractRecent progress of total syntheses in our laboratory has been described along with our background and methodologies. The target bioactive polyketides are classified into three categories according to their structures: (i) lactone‐fused polycyclic compounds [(+)‐cochleamycin A, (+)‐tubelactomicin A, and (−)‐tetrodecamycin], (ii) aromatic compounds [(−)‐tetracycline, (−)‐BE‐54238B, lymphostin, and (−)‐lagunamycin], and (iii) acyclic polyketides [xanthocillin X dimethylether, (+)‐trichostatin D, and (+)‐actinopyrone A]. Features of the total syntheses are described. Original methodologies have been developed and applied to construct the inherent structures of the target molecules. Most syntheses cited herein are the first total syntheses, and the absolute structures of the target molecules have been determined. © 2006 The Japan Chemical Journal Forum and Wiley Periodicals, Inc. Chem Rec 6: 217–233; 2006: Published online in Wiley InterScience (www.interscience.wiley.com) DOI 10.1002/tcr.20084
Inorganic functional materials: optimization of properties by structural and compositional control
Authors: West Anthony R. 
Published: August 2006

AbstractA review is given of the strategies used to dope inorganic solids and the consequences for properties such as ionic and electronic conductivity. Doping mechanisms involve either substitution of foreign ions onto lattice sites, creation of vacancies on either cation or anion sites, or population of normally empty interstitial sites by either anions or cations. Mechanisms for charge compensation associated with aliovalent doping are reviewed and examples are given in the fields of solid state ionics and high‐temperature superconductivity. The strategies used for targeting materials with new properties are reviewed, including a surprising number of cases where startling new properties are encountered in well‐known materials. Specific examples discussed include MgB2superconductor, Na β‐alumina sodium ion conductor, Ca12Al14O33oxide ion conductor, LiCoMnO4lithium battery cathode, doped Li4SiO4tunable lithium ion conductor, and La‐doped BaTiO3ferroelectric, which can be either semiconducting or insulating. Examples are also given of a curious observation that extraordinary properties are often encountered in materials that are on the edge of stability, either structurally or compositionally or at the crossover between different property types. © 2006 The Japan Chemical Journal Forum and Wiley Periodicals, Inc. Chem Rec 6: 206–216; 2006: Published online in Wiley InterScience (www.interscience.wiley.com) DOI 10.1002/tcr.20086
Aging-related temporal constraints to stability and instability in postural control
Authors: Slobounov Semyon M. , Haibach Pamela S. , Newell Karl M. 
Published: August 2006

Abstract
In this study, we review the evidence that older adults tend to have both a shorter time to lose stability in the maintenance of standing posture and the functionally related but inverse problem of needing more time to reacquire stability in transitioning to a postural state. These age-related time limitations to processes of stability are hypothesized to enhance the probability of falling with aging and the problems that can occur in the transition between activities, such as sitting to standing and standing to walking. The potential role of fitness and health variables in mediating the temporal constraints on the acquisition and loss of postural stability in aging is discussed.
Cell Detachment Model for an Antibody‐Based Microfluidic Cancer Screening System
Authors: Wankhede Swapnil P. , Du Zhiqiang , Berg Jordan M. , Vaughn Mark W. , Dallas Tim , Cheng Kwan H. , Gollahon Lauren 
Published: August 2006

AbstractWe consider cells bound to the floor of a microfluidic channel and present a model of their flow‐induced detachment. We approximate hydrodynamic force and cell elastic response using static finite‐element simulation of a single cell. Detachment is assumed to occur when hydrodynamic and adhesive forces are roughly equal. The result is extended to multiple cells at the device level using a sigmoidal curve fit. The model is applied to a microfluidic cancer‐screening device that discriminates between normal epithelial cells and cells infected with human papillomavirus (HPV), on the basis of increased expression of the transmembrane protein α6 integrin in the latter. Here, the cells to be tested are bound to a microchannel floor coated with anti α6 integrin antibodies. In an appropriate flow rate range, normal cells are washed away while HPV‐infected cells remain bound. The model allows interpolation between data points to choose the optimal flow rate and provides insight into interaction of cell mechanical properties and the flow‐induced detachment mechanism. Notably, the results suggest a significant influence of cell elastic response on detachment.
Identification of regulatory modules by co-clustering latent variable models: stem cell differentiation
Authors: Joung Je-Gun , Shin Dongho , Seong Rho Hyun , Zhang Byoung-Tak 
Published: August 2006

Abstract
Motivation: An important issue in stem cell biology is to understand how to direct differentiation towards a specific cell type. To elucidate the mechanism, previous studies have focused on identifying the responsible gene regulators, which have, however, failed to provide a systemic view of regulatory modules. To obtain a unified description of the regulatory modules, we characterized major stem cell species by employing a co-clustering latent variable model (LVM). The LVM-based method allowed us to elucidate the cell type-specific transcription factors, using genomic sequences as well as expression profiles.
Results: We used a list of genes enriched in each of 21 stem cell subpopulations, and their upstream genomic sequences. The LVM-based study allowed us to uncover the regulatory modules for each stem cell cluster, e.g. GABP and E2F for the proliferation phase, and Ap2α and Ap2γ for the quiescence phase. Furthermore, the identities of the stem cell clusters were well revealed by the constituent genes that were directly targeted by the modules. Consequently, our analytical framework was demonstrated to be useful through a detailed case study of stem cell differentiation and can be applied to problems with similar characteristics.
Contact: btzhang@bi.snu.ac.kr, rhseong@snu.ac.kr
Supplementary Information: Supplementary data are available at .
MLR-tagging: informative SNP selection for unphased genotypes based on multiple linear regression
Authors: He Jingwu , Zelikovsky Alexander 
Published: August 2006

Abstract
Summary: The search for the association between complex diseases and single nucleotide polymorphisms (SNPs) or haplotypes has recently received great attention. For these studies, it is essential to use a small subset of informative SNPs accurately representing the rest of the SNPs. Informative SNP selection can achieve (1) considerable budget savings by genotyping only a limited number of SNPs and computationally inferring all other SNPs or (2) necessary reduction of the huge SNP sets (obtained, e.g. from Affymetrix) for further fine haplotype analysis.
A novel informative SNP selection method for unphased genotype data based on multiple linear regression (MLR) is implemented in the software package MLR-tagging. This software can be used for informative SNP (tag) selection and genotype prediction. The stepwise tag selection algorithm (STSA) selects positions of the given number of informative SNPs based on a genotype sample population. The MLR SNP prediction algorithm predicts a complete genotype based on the values of its informative SNPs, their positions among all SNPs, and a sample of complete genotypes.
An extensive experimental study on various datasets including 10 regions from HapMap shows that the MLR prediction combined with stepwise tag selection uses fewer tags than the state-of-the-art method of Halperin et al. (2005).
Availability: MLR-Tagging software package is publicly available at
Contact: alexz@cs.gsu.edu
Robust inference of positive selection from recombining coding sequences
Authors: Scheffler Konrad , Martin Darren P. , Seoighe Cathal 
Published: August 2006

Abstract
Motivation: Accurate detection of positive Darwinian selection can provide important insights to researchers investigating the evolution of pathogens. However, many pathogens (particularly viruses) undergo frequent recombination and the phylogenetic methods commonly applied to detect positive selection have been shown to give misleading results when applied to recombining sequences. We propose a method that makes maximum likelihood inference of positive selection robust to the presence of recombination. This is achieved by allowing tree topologies and branch lengths to change across detected recombination breakpoints. Further improvements are obtained by allowing synonymous substitution rates to vary across sites.
Results: Using simulation we show that, even for extreme cases where recombination causes standard methods to reach false positive rates &gt;90%, the proposed method decreases the false positive rate to acceptable levels while retaining high power. We applied the method to two HIV-1 datasets for which we have previously found that inference of positive selection is invalid owing to high rates of recombination. In one of these (env gene) we still detected positive selection using the proposed method, while in the other (gag gene) we found no significant evidence of positive selection.
Availability: A HyPhy batch language implementation of the proposed methods and the HIV-1 datasets analysed are available at . The HyPhy package is available at , and it is planned that the proposed methods will be included in the next distribution. RDP2 is available at .
Contact: konrad@cbio.uct.ac.za, cathal@science.uct.ac.za
On‐call stress among Finnish anaesthetists*
Authors: Lindfors P. M. , Nurmi K. E. , Meretoja O. A. , Luukkonen R. A. , Viljanen A.‐M. , Leino T. J. , Härmä M I. 
Published: August 2006

SummaryWe investigated on‐call stress and its consequences among anaesthetists. A questionnaire was sent to all working Finnish anaesthetists (n = 550), with a response rate of 60%. Four categories of on‐call workload and a sum variable of stress symptoms were formed. The anaesthetists had the greatest on‐call workload among Finnish physicians. In our sample, 68% felt stressed during the study. The most important causes of stress were work and combining work with family. The study showed a positive correlation between stress symptoms and on‐call workload (p = 0.009). Moderate burnout was present in 18%vs 45% (p = 0.008) and exhaustion in 32% and 68% (p = 0.015), in the lowest vs highest workload category, respectively. The symptoms were significantly associated with stress, gender, perceived sleep deprivation, suicidal tendencies and sick leave. Being frequently on call correlates with severe stress symptoms and these symptoms are associated with sick leave.
Music therapy in the assessment and treatment of autistic spectrum disorder: clinical application and research evidence
Authors: Wigram T. , Gold C. 
Published: August 2006

AbstractBackground  Children and adolescents with autistic spectrum disorder (ASD) presenting with significant limitations in conventional forms of verbal and non‐verbal communication are found to respond positively to music therapy intervention involving both active, improvizational methods and receptive music therapy approaches. Improvizational musical activity with therapeutic objectives and outcomes has been found to facilitate motivation, communication skills and social interaction, as well as sustaining and developing attention. The structure and predictability found in music assist in reciprocal interaction, from which tolerance, flexibility and social engagement to build relationships emerge, relying on a systematic approach to promote appropriate and meaningful interpersonal responses.Results  Published reports of the value and effectiveness of music therapy as an intervention for children with ASD range from controlled studies to clinical case reports. Further documentation has emphasized the role music therapy plays in diagnostic and clinical assessment. Music therapy assessment can identify limitations and weaknesses in children, as well as strengths and potentials. Research evidence from a systematic review found two randomized controlled trials that examined short‐term effects of structured music therapy intervention. Significant effects were found in these studies even with extremely small samples, and the findings are important because they demonstrate the potential of the medium of music for autistic children. Case series studies were identified that examined the effects of improvizational music therapy where communicative behaviour, language development, emotional responsiveness, attention span and behavioural control improved over the course of an intervention of improvizational music therapy.
Medical investigation of children with autistic spectrum disorders
Authors: Cass H. , Sekaran D. , Baird G. 
Published: August 2006

AbstractFew well‐constructed studies have systematically evaluated medical investigation protocols for children with autistic spectrum disorders. This is in large part due to the heterogeneous nature of the population and changing diagnostic frameworks. This review outlines the studies that have directed investigation strategies to date, and discusses how these might be applied in the clinical situation. The importance of listing the conditions that may be present on the basis of the specific clinical presentation, and using a thorough history and examination to generate a pre‐test probability of the target disorders is emphasized if tests are to be useful in directing therapy or broader management approaches.
Development of an Internet‐based real‐time system for monitoring pharmacological interventions in children with neurodevelopmental and neuropsychiatric disorders
Authors: Gringras P. , Santosh P. , Baird G. 
Published: August 2006

AbstractFew children have a ‘pure’ diagnosis of neuropsychiatric disorders such as attention deficit hyperactivity disorder or autism. Most have complex, overlapping symptoms, and it is often these associated and common comorbidities that cause as much, if not more impairments, than the core symptoms. Prescribing decisions are therefore complex and made on the basis of eliciting a range of agreed ‘target symptoms’. At present, however, there are no agreed systems that allow monitoring of all areas of potential change, and few services are able to monitor symptoms, side effects, impact on family life and individual children’s quality of life systematically. At best many clinics use a plethora of paper‐based standardized questionnaires, based on individual diagnoses. This article describes the development of a novel biomedical informatics system that has been designed to allow parents, professionals and children to use a web‐based, real‐time symptom monitoring system to enable more effective treatments, better pathways of shared care, and more equitable and efficient service delivery for this group of vulnerable children.
Vaccines and the changing epidemiology of autism
Authors: Taylor B. 
Published: August 2006

AbstractBackground  The epidemiology of autism has been rather confusing, with very variable published prevalence figures and no clear incidence data. The cause of autism is unclear; vaccines have been incriminated.Methods  Literature review and interpretation.Results  The recorded prevalence of autism has increased considerably in recent years. This reflects greater recognition, with changes in diagnostic practice associated with more trained diagnosticians; broadening of diagnostic criteria to include a spectrum of disorder; a greater willingness by parents and educationalists to accept the label (in part because of entitlement to services); and better recording systems, among other factors. The cause(s) of autism remains unclear. There is a strong genetic component which, along with prenatally determined neuro‐anatomical/biochemical changes, makes any post‐natal ‘cause’ unlikely.Conclusions  There has (probably) been no real increase in the incidence of autism. There is no scientific evidence that the measles, mumps and rubella (MMR) vaccine or the mercury preservative used in some vaccines plays any part in the aetiology or triggering of autism, even in a subgroup of children with the condition.
Multidisciplinary assessment at a child development centre: do we conform to recommended standards?
Authors: Preece P. M. , Mott J. 
Published: August 2006

AbstractBackground  A proposed standard for the multidisciplinary assessment (MDA) of children with autism has been recently published by the National Autistic Society. This prompted a review of current practice at the child development centre in our local centre, to judge whether we were able to conform to the proposed national standard. The recommendation is that a child should complete a three‐stage assessment process from referral to completion of assessment within 30 weeks, with set times for completion of each stage (6, 7 and 17 weeks respectively). We applied this assessment model to children with a range of neurodevelopment problems, as the process of MDA is the same, irrespective of diagnosis.Methods  A retrospective analysis of medical and therapy records of all MDAs was carried out between April 2001 and March 2002.Results  In the 12‐month period studied, 52 MDAs were performed. Delays occurred, as judged by the standard, at all three stages of the assessment process. A total of 42% of children were seen within 6 weeks of initial referral, 37% within a further 7 weeks for specialist assessment, and 37% within a further 17 weeks for completion of MDA. As delays occurred at all stages, the cumulative total showed that only 19% of children completed all three stages within the recommended 30‐week standard. Barriers encountered included waiting times to see professionals, parental non‐attendance and prolonged assessment of complex problems. Some of these factors are outside our control, and on removing these factors the data were re‐analysed. This resulted in a slight improvement to 45%, 48% and 49% for completion of stages 1, 2 and 3 respectively. The major reason for delay remained the service capacity.Conclusion  In our experience the standards proposed by the National Autistic Society are not practical within present resources. We suggest that a reasonable expectation is to complete all assessments, from first concern to completed MDA, should be carried out within 52 weeks with present levels of resources. Any further improvement will require additional resources to reduce waiting times and increase the capacity.
What services do young children with autism spectrum disorder receive?
Authors: McConachie H. , Robinson G. 
Published: August 2006

AbstractBackground  In recent years, standards of good practice have been set for services to young children with autism spectrum disorders.Methods  Data were analysed on children’s use of local services during a 2‐year follow‐up of families involved in an evaluation of a group course for parents. Data collection began prior to publication of the standards.Results  Families’ reported experiences changed over time, but for most did not meet standards suggested: involvement with a multi‐agency team of professionals, having someone who acted as a key worker, and the child accessing 15 h per week of specialist provision.Conclusion  The development of flexible and responsive services appears to have a long way to go to meet standards set in the Autistic Spectrum Disorders Good Practice Guidance (2002) and the National Autism Plan for Children (2003).