bluuebunny/crossref_metadata_2025_split huggingface dataset:
Crystal engineering of the composition of pharmaceutical phases. 3. Primary amide supramolecular heterosynthons and their role in the design of pharmaceutical co-crystals
Authors: McMahon Jennifer A. , Bis Joanna A. , Vishweshwar Peddy , Shattock Tanise R. , McLaughlin Olga L. , Zaworotko Michael J. 
Published: April 2005

Abstract
A Cambridge Structural Database study of supramolecular synthons involving primary amides reveals that 84% form amide-amide dimers, whereas 14% form catemers in the absence of other competing hydrogen bond donors and/or acceptors. However in the presence of chemically different but complementary functional groups, e.g., carboxylic acids or aromatic nitrogen moieties, primary amides tend to form supramolecular heterosynthons. Supramolecular heterosynthons represent an opportunity for design of multi-component crystals (co-crystals) in which one molecule contains a primary amide and a second molecule (the co-crystal former) contains the functional group that is complementary to the primary amide. The results of the CSD analysis facilitated the selection of components for seven new primary amide co-crystals: A. Isonicotinamide/2-hydroxybenzoic acid (1:1); B. Nicotinäamide/3-hydroxybenzoic acid (1:1); C. Pyrazinamide/2,5-dihydroxybenzoic acid (1:1); D. Carbamazepine (CBZ)/4,4′-bipyridine (2:1); E. CBZ/4-aminobenzoic acid (2:1); F. CBZ/4-aminobenzoic acid/H2O (2:1:1); G. CBZ/2,6-pyridinedicarboxylic acid (1:1). The molecular recognition events involving the amide moieties are discussed in the context of our experimental results and their implications for crystal engineering of pharmaceutical co-crystals.
Neutron single crystal diffraction: techniques and applications in molecular systems
Authors: Wilson Chick C. 
Published: April 2005

Abstract
Single crystal neutron diffraction is a powerful method for the investigation of molecular structure, and in many cases is found to be an excellent complement to X-ray diffraction. The ability of neutron diffraction to determine the position of the atomic nucleus, rather than the electron density, is key to its use in structural studies. Among other advantages, this lends the neutron the ability to determine accurately the positions (and displacement parameters) of light atoms. In the context of molecular systems, neutron diffraction is thus very well suited to the determination of hydrogen atom parameters, which are key to many applications in molecular structure determination, including hydrogen bonded systems, organometallic materials and in macromolecular structures.
This article briefly summarises some of the applications to which single crystal neutron diffraction has been put in the study of molecular structure, together with an account of the techniques and instrumentation used for these experiments. Particular account is taken of recent developments in instrumentation, and the new scientific applications that have resulted from these, along with a forward look to some of the exciting developments currently taking place in this field. These include instruments with dramatically enhanced detector arrays, other optimisations to improve count-rate and performance, the construction of new neutron sources and exciting new instruments being planned for these sources.
Combined Linkage and Association Mapping of Quantitative Trait Loci by Multiple Markers
Authors: Jung Jeesun , Fan Ruzong , Jin Lei 
Published: April 2005

Abstract
Using multiple diallelic markers, variance component models are proposed for high-resolution combined linkage and association mapping of quantitative trait loci (QTL) based on nuclear families. The objective is to build a model that may fully use marker information for fine association mapping of QTL in the presence of prior linkage. The measures of linkage disequilibrium and the genetic effects are incorporated in the mean coefficients and are decomposed into orthogonal additive and dominance effects. The linkage information is modeled in variance-covariance matrices. Hence, the proposed methods model both association and linkage in a unified model. On the basis of marker information, a multipoint interval mapping method is provided to estimate the proportion of allele sharing identical by descent (IBD) and the probability of sharing two alleles IBD at a putative QTL for a sib-pair. To test the association between the trait locus and the markers, both likelihood-ratio tests and F-tests can be constructed on the basis of the proposed models. In addition, analytical formulas of noncentrality parameter approximations of the F-test statistics are provided. Type I error rates of the proposed test statistics are calculated to show their robustness. After comparing with the association between-family and association within-family (AbAw) approach by Abecasis and Fulker et al., it is found that the method proposed in this article is more powerful and advantageous based on simulation study and power calculation. By power and sample size comparison, it is shown that models that use more markers may have higher power than models that use fewer markers. The multiple-marker analysis can be more advantageous and has higher power in fine mapping QTL. As an application, the Genetic Analysis Workshop 12 German asthma data are analyzed using the proposed methods.
A Postsynaptic Role for Rhp55/57 That Is Responsible for Cell Death in Δrqh1 Mutants Following Replication Arrest in Schizosaccharomyces pombe
Authors: Hope Justin C , Maftahi Mohamed , Freyer Greg A 
Published: April 2005

AbstractFollowing replication arrest, multiple cellular responses are triggered to maintain genomic integrity. In fission yeast, the RecQ helicase, Rqh1, plays a critical role in this process. This is demonstrated in Δrqh1 cells that, following treatment with hydroxyurea (HU), undergo an aberrant mitosis leading to cell death. Previous data suggest that Rqh1 functions with homologous recombination (HR) in recovery from replication arrest. We have found that loss of the HR genes rhp55+ or rhp57+, but not rhp51+ or rhp54+, suppresses the HU sensitivity of Δrqh1 cells. Much of this suppression requires Rhp51 and Rhp54. In addition, this suppression is partially dependent on swi5+. In budding yeast, overexpressing Rad51 (the Rhp51 homolog) minimized the need for Rad55/57 (Rhp55/57) in nucleoprotein filament formation. We overexpressed Rhp51 in Schizosaccharomyces pombe and found that it greatly reduced the requirement for Rhp55/57 in recovery from DNA damage. However, overexpressing Rhp51 did not change the Δrhp55 suppression of the HU sensitivity of Δrqh1, supporting an Rhp55/57 function during HR independent of nucleoprotein filament formation. These results are consistent with Rqh1 playing a role late in HR following replication arrest and provide evidence for a postsynaptic function for Rhp55/57.
A Genomics Approach to the Detection of Positive Selection in Cattle:
Authors: Lynn David J , Freeman Abigail R , Murray Caitriona , Bradley Daniel G 
Published: April 2005

Abstract
The detection of adaptive evolution at the molecular level is of interest not only as an insight into the process of evolution but also because of its functional implications for genes of interest. Here, we present the first genomics approach to detecting positive selection operating on the Bos taurus lineage, an important domestic species. This analysis led to the identification of the T-cell and natural killer (NK) cell receptor cluster of differentiation 2 (CD2) as having a strong signal of selection. Further detailed investigation of CD2 revealed that this gene was subject to positive selection during the evolution of a number of mammalian lineages. Moreover, we show that selection has operated primarily on the extracellular domain of CD2 and discuss the implications of this for an important regulator of the adaptive immune response.
Subdivision of Large Introns in Drosophila by Recursive Splicing at Nonexonic Elements
Authors: Burnette James M , Miyamoto-Sato Etsuko , Schaub Marc A , Conklin Jamie , Lopez A Javier 
Published: April 2005

Abstract
Many genes with important roles in development and disease contain exceptionally long introns, but special mechanisms for their expression have not been investigated. We present bioinformatic, phylogenetic, and experimental evidence in Drosophila for a mechanism that subdivides many large introns by recursive splicing at nonexonic elements and alternative exons. Recursive splice sites predicted with highly stringent criteria are found at much higher frequency than expected in the sense strands of introns &gt;20 kb, but they are found only at the expected frequency on the antisense strands, and they are underrepresented within introns &lt;10 kb. The predicted sites in long introns are highly conserved between Drosophila melanogaster and Drosophila pseudoobscura, despite extensive divergence of other sequences within the same introns. These patterns of enrichment and conservation indicate that recursive splice sites are advantageous in the context of long introns. Experimental analyses of in vivo processing intermediates and lariat products from four large introns in the unrelated genes kuzbanian, outspread, and Ultrabithorax confirmed that these introns are removed by a series of recursive splicing steps using the predicted nonexonic sites. Mutation of nonexonic site RP3 within Ultrabithorax also confirmed that recursive splicing is the predominant processing pathway even with a shortened version of the intron. We discuss currently known and potential roles for recursive splicing.
Interaction of the Saccharomyces cerevisiae Cortical Actin Patch Protein Rvs167p With Proteins Involved in ER to Golgi Vesicle Trafficking
Authors: Friesen Helena , Colwill Karen , Robertson Karen , Schub Oliver , Andrews Brenda 
Published: April 2005

Abstract
We have used affinity chromatography to identify two proteins that bind to the SH3 domain of the actin cytoskeleton protein Rvs167p: Gyp5p and Gyl1p. Gyp5p has been shown to be a GTPase activating protein (GAP) for Ypt1p, a Rab GTPase involved in ER to Golgi trafficking; Gyl1p is a protein that resembles Gyp5p and has recently been shown to colocalize with and belong to the same protein complex as Gyp5p. We show that Gyl1p and Gyp5p interact directly with each other, likely through their carboxy-terminal coiled-coil regions. In assays of GAP activity, Gyp5p had GAP activity toward Ypt1p and we found that this activity was stimulated by the addition of Gyl1p. Gyl1p had no GAP activity toward Ypt1p. Genetic experiments suggest a role for Gyp5p and Gyl1p in ER to Golgi trafficking, consistent with their biochemical role. Since Rvs167p has a previously characterized role in endocytosis and we have shown here that it interacts with proteins involved in Golgi vesicle trafficking, we suggest that Rvs167p may have a general role in vesicle trafficking.
Mutations in Snail Family Genes Enhance Craniosynostosis of Twist1 Haplo-insufficient Mice
Authors: Oram Kathleen F , Gridley Thomas 
Published: April 2005

Abstract
In Drosophila, mutations in the Twist gene interact with mutations in the Snail gene. We show that the mouse Twist1 mutation interacts with Snai1 and Snai2 mutations to enhance aberrant cranial suture fusion, demonstrating that genetic interactions between genes of the Twist and Snail families have been conserved during evolution.
Attributable Cost of Nosocomial Primary Bloodstream Infection in Pediatric Intensive Care Unit Patients
Authors: Elward Alexis M. , Hollenbeak Christopher S. , Warren David K. , Fraser Victoria J. 
Published: April 2005

Objective. To determine the attributable cost of nosocomial primary bloodstream infections (BSIs) in PICU patients.
Methods. A prospective cohort study was conducted of the PICU of the St Louis Children's Hospital, a 235-bed academic tertiary care center. All patients who were admitted to the PICU were included unless they met the following exclusion criteria: age &gt;18 years, death within 24 hours of PICU admission, admission to the NICU service. Total and direct medical costs of PICU and hospital stay for patients with and without nosocomial primary BSI were measured.
Results. Fifty-seven children developed 65 episodes of primary BSIs during their PICU stay. The rate of BSI in this population was 13.8 per 1000 central venous catheter days. In multiple linear regression analysis, severity of illness as measured by the admission Pediatric Risk of Mortality Score III, congenital heart disease, underlying lung disease, ventilator days, transplant (solid organ and bone marrow), and nosocomial primary BSI were independent predictors of PICU direct costs. The direct cost of PICU admission for patients with nosocomial primary BSI was $45 615 and for the patients without primary BSI was $6396.
Conclusions. After controlling for age, severity of illness, underlying disease, and ventilator days, we found that the direct cost of PICU admission attributable to nosocomial primary BSI was $39 219. The prevention of these infections through specific interventions is likely to be cost-effective.
Teen Reach: Outcomes From a Randomized, Controlled Trial of a Tobacco Reduction Program for Teens Seen in Primary Medical Care
Authors: Hollis Jack F. , Polen Michael R. , Whitlock Evelyn P. , Lichtenstein Edward , Mullooly John P. , Velicer Wayne F. , Redding Colleen A. 
Published: April 2005

Objective. To test the long-term efficacy of brief counseling plus a computer-based tobacco intervention for teens being seen for routine medical care.
Methods. Both smoking and nonsmoking teens, 14 to 17 years of age, who were being seen for routine visits were eligible for this 2-arm controlled trial. Staff members approached teens in waiting rooms of 7 large pediatric and family practice departments within a group-practice health maintenance organization. Of 3747 teens invited at ≥1 visits, 2526 (67%) consented and were randomized to tobacco intervention or brief dietary advice. The tobacco intervention was individually tailored on the basis of smoking status and stage of change. It included a 30-second clinician advice message, a 10-minute interactive computer program, a 5-minute motivational interview, and up to two 10-minute telephone or in-person booster sessions. The control intervention was a 5-minute motivational intervention to promote increased consumption of fruits and vegetables. Follow-up smoking status was assessed after 1 and 2 years.
Results. Abstinence rates after 2 years were significantly higher for the tobacco intervention arm, relative to the control group, in the combined sample of baseline smokers and nonsmokers (odds ratio [OR]: 1.23; 95% confidence interval [CI]: 1.03–1.47). Treatment effects were particularly strong among baseline self-described smokers (OR: 2.42; 95% CI: 1.40–4.16) but were not significant for baseline nonsmokers (OR: 1.25; 95% CI: 0.97–1.61) or for those who had “experimented” in the past month at baseline (OR: 0.95; 95% CI: 0.45–1.98).
Conclusions. Brief, computer-assisted, tobacco intervention during routine medical care increased the smoking cessation rate among self-described smokers but was less effective in preventing smoking onset.
Have There Been Changes in Children's Psychosomatic Symptoms? A 10-Year Comparison From Finland
Authors: Santalahti Paivi , Aromaa Minna , Sourander Andre , Helenius Hans , Piha Jorma 
Published: April 2005

Objectives. The aims of the study were to determine whether the prevalence of children's somatic symptoms, such as headache, abdominal pain, other pain, and nausea and vomiting, changed from 1989 to 1999 and to study the similarity of parents' and children's reports of the child's symptoms. Furthermore, the aims were to explore possible comorbidity in somatic symptoms and to investigate the associations between somatic and psychiatric symptoms.Methods. Two cross-sectional, representative samples were compared. All children born in 1981 (1989 sample, n = 985) and 1991 (1999 sample, n = 962) and living in selected school districts in southwest Finland served as study samples. The response rate for the 1989 sample was 95% and that for the 1999 sample was 86%. Both children and parents were asked about the children's somatic symptoms, whereas parents, children, and teachers were asked about psychiatric symptoms. To study psychiatric symptoms, the Children's Depression Inventory and Rutter's parent and teacher scales were used.Results. The prevalence of frequent headaches and abdominal pain increased somewhat from 1989 to 1999. Parents often failed to recognize their children's psychosomatic problems. Child-reported somatic symptoms were associated with conduct and hyperactivity symptoms, in addition to a previously well-documented association with depression. In associations between somatic symptoms and psychiatric symptoms, there were some differences between the 1989 and 1999 samples.Conclusions. In clinical work, questions about somatic and psychiatric symptoms should also be addressed to children themselves, because parents and teachers do not always recognize children's symptoms. When somatic problems are being evaluated, psychiatric symptoms should be asked about, and vice versa. More research is needed to explore the reasons for the increased prevalence of somatic symptoms and their associations with psychiatric symptoms.
Effects of Race, Insurance Status, and Hospital Volume on Perforated Appendicitis in Children
Authors: Smink Douglas S. , Fishman Steven J. , Kleinman Ken , Finkelstein Jonathan A. 
Published: April 2005

Objective. Previous research suggests that perforated appendicitis is more common in Medicaid patients, but the roles of minority race and hospital volume remain largely unstudied. We sought to investigate the association of perforated appendicitis in children with minority race, insurance status, and hospital volume.Methods. We conducted a retrospective, population-based cohort study of 33184 children who had an International Classification of Diseases, Ninth Revision diagnosis code for acute appendicitis in The Kids' Inpatient Database, a pediatric database from 22 states in 1997. A multivariate logistic regression model was developed to determine patient and hospital characteristics predictive of perforated appendicitis.Results. Of 33184 children with acute appendicitis, 10777 (32.5%) were perforated. In multivariate analysis, black (odds ratio [OR]: 1.24; 95% confidence interval [CI]: 1.10–1.39) and Hispanic (OR: 1.19; 95% CI: 1.10–1.29) children were more likely to have perforated appendicitis than white children. Perforation was also more likely in Medicaid patients (OR: 1.30; 95% CI 1.22–1.39) compared with privately insured children. Annual hospital volume of cases of appendicitis was not significantly associated with perforation in multivariate analysis.Conclusions. Perforated appendicitis disproportionately affected both children of minority race and children insured by Medicaid. No effect of hospital volume was observed. To reduce this racial disparity, efforts should focus on the causes of delayed diagnosis and the treatment of appendicitis in children of minority race.
Ensuring Accurate Knowledge of Prematurity Outcomes for Prenatal Counseling
Authors: Blanco Fermin , Suresh Gautham , Howard Diantha , Soll Roger F. 
Published: April 2005

Objectives. To determine the accuracy of knowledge of different health care providers regarding survival and long-term morbidity rates for very premature infants and to examine whether a focused educational intervention improves the accuracy of this knowledge and influences health care decisions.Methods. Using hypothetical case scenarios with infants at ≤28 weeks of gestation, we surveyed a variety of caregivers involved in perinatal communication and decision-making processes at a tertiary center that provides intensive care for neonates. We asked physicians from the pediatrics and obstetrics services and nurses and nurse practitioners from the NICU and obstetrics ward for their best estimates of survival and major long-term disability rates and for their opinions regarding the appropriateness of resuscitation and life support at each week of gestation of &lt;29 weeks. After the survey, we educated all providers about current data on survival and long-term disability rates for preterm infants and gave them pocket-sized cards summarizing this information for reference during prenatal counseling. One month after the educational intervention and complete dissemination of the cards, a questionnaire with questions identical to those in the first survey was mailed to the same individuals.Results. Fifty-one health care providers were involved in the baseline survey. The response rates for the postintervention survey were 100% for physicians (20 of 20 subjects) and nurses (20 of 20 subjects) and 91% (10 of 11 subjects) for the nurse practitioners. In the baseline survey, statistically significant underestimates of survival rates were seen for physicians and nurses at 23 to 28 weeks of gestation and for nurse practitioners at 23 to 27 weeks of gestation. Statistically significant overestimates of disability rates were seen for physicians and nurse practitioners at ≤26 weeks of gestation and for nurses at ≤28 weeks of gestation. After the intervention, respondents demonstrated significant improvements in the accuracy of survival and disability estimates at many, but not all, gestational ages. Although underestimation of survival rates and overestimation of disability rates decreased after the intervention, it persisted to some degree. After the intervention, a larger proportion of physicians (53% vs 21%) and a smaller proportion of nurses (10% vs 37%) were likely to recommend resuscitation for infants born at 23 weeks of gestation.Conclusions. Physicians, nurses, and nurse practitioners underestimated survival rates and overestimated long-term disability rates for very premature infants. After education, their estimates of survival and long-term disability rates for these infants improved significantly. More accurate estimates of survival and disability rates affected physicians' and nurses' theoretical decision-making regarding the appropriateness of resuscitation at 23 weeks of gestation.