bluuebunny/crossref_metadata_2025_split huggingface dataset:
Characterization of sequence variability in nucleosome core histone folds
Authors: Sullivan Steven A. , Landsman David 
Published: July 2003

AbstractThe three‐helix, ∼65‐residue histone fold domain is the most structurally conserved part of the core histones H2A, H2B, H3, and H4. However, it evinces a notable degree of sequence variation within and between histone classes. We used two approaches to characterize sequence variation in these histone folds, toward elucidating their structure/function relationships and evolution. On the one hand we asked how much of the sequence variation seen in structure‐based alignments of the folds maintains physicochemical properties at a position, and on the other, whether conservation correlates to structural importance, as measured by the number of residue‐to‐residue contacts a position makes. Strong physicochemical conservation or correlation of conservation to contacts would support the idea that functional constraints, rather than genetic drift, determines the observed range of variants at a given position. We used an 11‐state table of physicochemical properties to classify each position in the core histone fold (CHF) alignments, and a public website (http://www.ebi.ac.uk/thornton‐srv/databases/cgi‐bin/valdar/scorecons_server.pl) to score conservation. We found that, depending on histone class, from 38 to 77% of CHF positions are maximally conserved physicochemically, and that for H2B, H3, and H4 the degree to which a position is conserved correlates positively to the number of contacts made by the residue at that position in the crystal structure of the nucleosome core particle. We also examined the correlation between conservation and the type of contact (e.g., inter‐ or intrachain, histone‐histone, or histone‐DNA, etc.). For H2B, H3, and H4 we found a positive correlation between conservation and number of interchain protein contacts. No such correlation or statistical significance was found for DNA or intrachain contacts. This suggests that variations in the CHF sequences could be functionally constrained by requirements to make sufficient interchain histone contacts. We also suggest that inventory of histone residue variants can augment functional studies of histones. An example is presented for histone H3. Proteins 2003;52:454–465. © 2003 Wiley‐Liss, Inc.
Exploring the origin of the ion selectivity of the KcsA potassium channel
Authors: Burykin Anton , Kato Mitsunori , Warshel Arieh 
Published: July 2003

AbstractThe availability of structural information about biological ion channels provides an opportunity to gain a detailed understanding of the control of ion selectivity by biological systems. However, accomplishing this task by computer simulation approaches is very challenging. First, although the activation barriers for ion transport can be evaluated by microscopic simulations, it is hard to obtain accurate results by such approaches. Second, the selectivity is related to the actual ion current and not directly to the individual activation barriers. Thus, it is essential to simulate the ion currents and this cannot be accomplished at present by microscopic MD approaches. In order to address this challenge, we developed and refined an approach capable of evaluating ion current while still reflecting the realistic features of the given channel. Our method involves generation of semimacroscopic free energy surfaces for the channel/ions system and Brownian dynamics (BD) simulations of the corresponding ion current. In contrast to most alternative macroscopic models, our approach is able to reproduce the difference between the free energy surfaces of different ions and thus to address the selectivity problem. Our method is used in a study of the selectivity of the KcsA channel toward the K+ and Na+ ions. The BD simulations with the calculated free energy profiles produce an appreciable selectivity. To the best of our knowledge, this is the first time that the trend in the selectivity in the ion current is produced by a computer simulation approach. Nevertheless, the calculated selectivity is still smaller than its experimental estimate. Recognizing that the calculated profiles are not perfect, we examine how changes in these profiles can account for the observed selectivity. It is found that the origin of the selectivity is more complex than generally assumed. The observed selectivity can be reproduced by increasing the barrier at the exit and the entrance of the selectivity filter, but the necessary changes in the barrier approach the limit of the error in the PDLD/S‐LRA calculations. Other options that can increase the selectivity are also considered, including the difference between the Na+…Na+ and K+…K+ interaction. However, this interesting effect does not appear to lead to a major difference in selectivity since the Na+ ions at the limit of strong interaction tend to move in a less concerted way than the K+ ions. Changes in the relative binding energies at the different binding sites are also not so effective in changing the selectivity. Finally, it is pointed out that using the calculated profiles as a starting point and forcing the model to satisfy different experimentally based constraints, should eventually provide more detailed understanding of the different complex factors involved in ion selectivity of biological channels. Proteins 2003;52:412–426. © 2003 Wiley‐Liss, Inc.
Neural Networks in 3D QSAR
Authors: Livingstone David J. , Manallack David T. 
Published: July 2003

Abstract3D QSAR data analysis typically deals with large numbers of descriptors and various methods have been used to cope with this multivariate problem. One popular method, CoMFA, makes use of Partial Least Squares (PLS) regression. Alternative methods of data analysis to PLS have been explored including artificial neural networks (ANN). Within 3D QSAR, ANNs have been successful in producing models showing reasonable predictive capabilities. This review will examine recent studies in 3D QSAR and QSPR using ANN methods.
Structure Activity Relationships (SAR) and Pharmacophore Discovery Using Inductive Logic Programming (ILP)
Authors: Sternberg Michael J. E. , Muggleton Stephen H. 
Published: July 2003

AbstractThe application of Inductive Logic Programming (ILP), a form of machine learning, to derive structure activity relationships (SAR) and to discover pharmacophores is reported. The ILP approach was initially applied to model 1D SARs in terms of the attributes of the molecules. Subsequently 2D ILP SARs were developed describing chemical connectivity. Finally ILP has been used to model 3D SARs in which the conformation of the pharmacophore can be described. ILP has advantages over many other widely used methods as it can reason with relations and hence discover chemical substructures and 3D features without these aspects having been explicitly encoded prior to learning. In particular, there is no requirement for a structural superposition. Additionally, the results of ILP provide chemical descriptions that can readily be understood by a medicinal chemist. In several trials, ILP‐based SARs have been shown to be significantly more accurate than widely‐used methods.
Analysis of clustered matched‐pair data
Authors: Durkalski Valerie L. , Palesch Yuko Y. , Lipsitz Stuart R. , Rust Philip F. 
Published: July 2003

AbstractEvaluation of the performance of a new diagnostic procedure with respect to a standard procedure arises frequently in practice. The response of interest, often in a dichotomous form, is measured twice, once with each procedure. The two procedures are administered to either two matched individuals, or when practical, to the same individual. A large sample test for matched‐pair data is the McNemar test. The main assumption of this test is independent paired responses; however, when more than one outcome from an individual is measured by each procedure, the data are clustered. Examples of such cases can be seen in dental and ophthalmology studies. Variance adjustment methods for the analysis of clustered matched‐pair data have been proposed; however, because of unequal cluster sizes, variability of correlation structures within a cluster (within paired responses in a cluster as well as between paired responses in a cluster), and unequal success probabilities among the clusters, the performances of some available methods are not consistent. This research proposes a simple adjustment to the McNemar test for the analysis of clustered matched‐pair data. Method of moments is used to calculate a consistent variance estimator. Using Monte Carlo simulation, the size and power of the proposed test are compared to those of two currently available methods. To illustrate practical application, clustered matched‐pair data from two clinical studies are analysed. Copyright © 2003 John Wiley & Sons, Ltd.
The role of professional associations in reducing maternal mortality worldwide
Authors: Chamberlain J. , McDonagh R. , Lalonde A. , Arulkumaran S. 
Published: July 2003

AbstractThe death of hundreds of thousands of women due to pregnancy‐related complications casts a shadow over the modern obstetrical world. This paper examines the potential roles and responsibilities of professional obstetrical and midwifery associations in addressing this tolerated tragedy of maternal deaths. We examine the successes and challenges of obstetrical and midwifery associations and encourage the growth and development of active associations to address maternal mortality within their own borders. Professional associations can play a vital role in the reduction of maternal mortality worldwide. Their roles include lobbying for women's health and rights, setting standards of practice, raising awareness and team building. Associations from developed countries can influence and strengthen their colleagues within developing countries; for example, the FIGO Save the Mothers initiative. Professional associations should be encouraged to play an active role in reducing maternal mortality within their own country and abroad.
Evaluation of the Balloon Analogue Risk Task (BART) as a predictor of adolescent real‐world risk‐taking behaviours
Authors: Lejuez C.W. , Aklin Will M. , Zvolensky Michael J. , Pedulla Christina M. 
Published: July 2003

AbstractThe Balloon Analogue Risk Task (BART) was administered to a sample of 26 high school‐aged adolescents to test the utility of the BART as a behavioural measure of risk‐taking propensity. Data indicate that riskyness on the BART was related to self‐reported engagement in real‐world risk‐taking behaviours. These data replicate and uniquely extend past research to an adolescent sample, suggesting that the BART may be a useful addition to self‐report batteries for the assessment of risk‐taking behaviours in adolescents.
Chemical inhibitors of cyclin‐dependent kinases control proliferation, apoptosis and differentiation of oligodendroglial cells
Authors: Nguyen Laurent , Malgrange Brigitte , Rocher Véronique , Hans Grégory , Moonen Gustave , Rigo Jean‐Michel , Belachew Shibeshih 
Published: July 2003

AbstractSince cyclin‐dependent kinases (Cdks) and their endogenous inhibitors (Cdkis) play an essential role as regulators of cell cycle withdrawal and onset of differentiation within oligodendroglial cells, we assessed here the effects of exogenous chemical Cdk inhibitors (CKIs) on cultured rat cortical oligodendrocyte progenitor cells (OPCs). We showed that purine derivatives and especially roscovitine strongly inhibited OPCs proliferation. In the presence of mitogenic signals, roscovitine synergized with thyroid hormone to stimulate oligodendrocyte differentiation. Roscovitine also prevented oligodendroglial apoptosis induced by growth factor deprivation. We thus demonstrated that small molecular weight chemical CKIs have important effects on crucial events of oligodendroglial development in vitro. This might open prospects for using these apparently well tolerated agents in remyelination strategies.
Utilization of discards and offal from commercial fisheries by seabirds in the Baltic Sea
Authors: Garthe Stefan , Scherp Birgit 
Published: July 2003

AbstractThe distribution and abundance of scavenging seabirds and their utilization of discards and offal between June and December 1998 were studied in the western Baltic Sea. Herring gulls were clearly the most numerous scavenging species in all areas and all seasons, followed by great black-backed gulls, lesser black-backed gulls and mew gulls. High percentages of discarded gadoids (cod, whiting), clupeids (herring, sprat), scad, rockling and offal were consumed by seabirds during experimental discarding on fishing boats, whereas the percentages of flatfish consumed were extremely low. There was a clear effect of cod length on total and species-specific consumption by birds but this pattern was hardly evident for clupeids or dab. By combining official discard and offal statistics and our experimental discarding, we estimate that 6500 t of fish discards and 16 000 t of offal were consumed annually by seabirds in the Baltic Sea. Bivalves, especially blue mussels Mytilus edulis, were the most frequently represented food item in herring gull pellets. Fish identified in the pellets consisted mainly of gadoids, in particular cod. The proportion of discards in herring gull pellets was on average 1.6% (range: 0–4.5%) at Laboe and 17.5% at Warnemünde (range: 9.4–25.5%), but pellets bias diet assessment as offal and other soft prey (including clupeids) will be under-represented. Scavenging on discards and offal is a widespread phenomenon in the Baltic Sea as it is in other shelf areas of Europe, but the number of bird species involved is generally lower and strongly biased towards gulls, especially herring gulls.
The effects of swimbladder size, condition and gonads on the acoustic target strength of mature capelin
Authors: Jørgensen Roar 
Published: July 2003

Abstract
Pre- and post-spawning capelin from the Barents Sea stock were observed in a net pen with a calibrated 38 kHz scientific split-beam echosounder. The transducer was positioned vertically or tilted. The acoustic target strength (TS) of capelin depended on swimbladder length. In female capelin within 15.5–18.0 cm length the logarithm of weight was significantly negatively related to TS. The negative effect of weight on TS could be due to a higher condition factor (assumed higher fat content), which gave the fish additional buoyancy and less need for swimbladder volume. The effect of gonad weight on TS was not significant. Comparisons of measurements made with vertical and tilted transducers demonstrated a small but significant effect of tilt angle on TS.
Redistribution of motor proteins by Cytochalasin J treatment
Authors: Robinson Rollin W. , Snyder Judith A. 
Published: July 2003

AbstractIn this study we extend our analysis of the effect of Cytochalasin J (CJ) on mitotic and interphase cells by the use of immunocytochemical techniques to localize antigens to anti‐β‐tubulin, anti‐dynein heavy chain (HC), anti‐dynein intermediate chain (IC), and anti‐kinesin antibodies following CJ treatment. Anti‐dynein IC and HC staining of CJ treated cells showed a significant reduction in anti‐dynein staining in the nuclear region of interphase cells. Monolayer cultures of PtK1cells treated with 10 μg/ml CJ for 10 min showed a significant reduction in pixel luminosity of fluorescence staining using anti‐dynein IC and HC antibodies (P<0.05). Cytochalasin J treatment reorganized anti‐dynein staining from a cytoplasmic punctate staining with greatest intensity in the perinuclear region, to a more uniform staining throughout the cytoplasm.
In vitro T‐cell responses to β‐lactam drugs in immediate and nonimmediate allergic reactions
Authors: Luque I. , Leyva L. , José Torres M. , Rosal M. , Mayorga C. , Segura J. M. , Blanca M. , Juárez C. 
Published: July 2003

Background:β‐Lactam drugs may induce both cellular and humoral allergic reactions, and there is evidence that T cells play an important role in the pathogenesis of these reactions. The aim of this work was to assess the sensitivity and specificity of the lymphocyte transformation test (LTT) as an in vitro diagnostic tool, in patients with either an immediate or a nonimmediate reaction to penicillin G and/or amoxicillin. Methods: Fifty patients with a well‐documented history of allergic reactions to β‐lactams (31 immediate and 19 nonimmediate) were studied by means of skin tests (prick and intradermal), radioallergosorbent test (RAST), and, when necessary, controlled administration of the drug. Twenty‐eight healthy subjects with good tolerance to penicillins served as controls. LTT was performed in all subjects. Results: Skin tests were positive in 77.4% of the patients with immediate reactions and in 36.8% of those with nonimmediate reactions. The overall sensitivity of LTT in the allergic patients was 62%, but, when analyzed separately, sensitivity was 64.5% for the immediate group and 57.9% for the nonimmediate group. The LTT specificity was 92.8%. Conclusions: The LTT should be considered a useful in vitro diagnostic tool to identify subjects allergic to penicillins, especially patients with nonimmediate reactions where the LTT has a better diagnostic value than skin tests. Interestingly, positive T‐cell proliferative responses can be observed 10 or more years after the occurrence of the reaction without further exposure to the drug.
Screening for diabetic retinopathy by non‐ophthalmologists: an effective public health tool
Authors: Verma Lalit , Prakash Gunjan , Tewari Hem K. , Gupta Sanjeev K. , Murthy G. V. S. , Sharma Nisha 
Published: July 2003

Abstract.Purpose:  To investigate and report the reliability of detection and grading of diabetic retinopathy by direct ophthalmoscopy through a dilated pupil by general physicians (non‐ophthalmologists) and optometrists who have undergone a short period of training.Methods:  A total of 400 eyes of 200 diabetes patients were examined by two non‐ophthalmologists. Their observations were compared with an ophthalmologist's diagnoses for the same patients.Results:  The diagnoses made by the general physician (kappa = 0.8381, SE = 0.041) and the optometrist (kappa = 0.7186, SE = 0.051) showed good rates of agreement with the ophthalmologist's diagnoses.Conclusions:  The provision of appropriate screening protocols and follow‐up parameters can enable primary care physicians and support personnel to reliably screen individuals for retinopathy in diabetes. This will reduce the workload of tertiary hospitals, and provide optimal services to the huge majority of the Indian population that has limited access to eye care services.
Timolol 0.5%/dorzolamide 2% fixed combination versus timolol 0.5%/pilocarpine 2% fixed combination in primary open‐angle glaucoma or ocular hypertensive patients
Authors: Kałuz̊ny Jakub J. , Szaflik Jerzy , Czechowicz‐Janicka Krystyna , Kałuz̊ny Józef , Orzalkiewicz Alicja , Zaleska Anna , Krajewska Malgorzata , Stewart Jeanette A. , Leech Jessica N. , Stewart William C. 
Published: July 2003

Abstract.Purpose:  To establish the efficacy and safety of timolol maleate/dorzolamide fixed combination (TDFC) versus timolol maleate/pilocarpine fixed combination (TPFC), each given twice daily, in primary open‐angle glaucoma or ocular hypertensive patients.Methods:  In this prospective, multicentred, double‐masked trial, 37 patients were treated twice daily with timolol for 4 weeks. They were then randomized to one of the treatment medications for 6 weeks, after which they were treated with timolol again for 2 weeks before being placed on the opposite treatment medication for 6 weeks.Results:  A total of 36 patients completed the trial. Their mean baseline intraocular pressure (IOP) was 22.3 ± 3.7 mmHg. Following 6 weeks of treatment, the mean trough (08.00 hours) IOP was 18.0 ± 2.2 mmHg for TDFC and 17.4 ± 2.0 mmHg for TPFC (p = 0.22). The mean diurnal curve IOP was 18.1 ± 2.2 mmHg for TDFC and 16.7 ± 1.9 mmHg for TPFC (p = 0.0007). At the remaining time‐points (10.00, 18.00 and 20.00 hours), TPFC IOPs were statistically lower than TDFC IOPs (p < 0.03). There were statistically more unsolicited reports of vision change and ocular pain associated with TPFC (p = 0.04). Six patients were discontinued early from TPFC therapy (17%) versus two from TDFC (6%) (p = 0.13).Conclusions:  This study suggests that TPFC can provide at least a similar efficacious reduction in IOP as TDFC in patients with primary open‐angle glaucoma or ocular hypertension.
Viscocanalostomy and deep sclerectomy for the surgical treatment of glaucoma: a longterm follow‐up
Authors: Wishart Peter K. , Wishart Manijeh S. , Porooshani Hamid 
Published: July 2003

Abstract.Purpose:  To study the outcome of viscocanalostomy (VC) and deep sclerectomy (DS) for the surgical management of medically uncontrolled glaucoma.Patients and Methods:  A non‐randomized, prospective study of all consecutive non‐penetrating glaucoma filtering procedures was carried out in two centres. In the first centre, one surgeon (MSW) performed VC in 105 eyes (27 VC and 78 phaco VC). In the second centre, one surgeon (PKW) performed DS in 87 eyes (52 DS and 35 phaco DS).Results:  The mean follow‐up was 36 months (range 9–60 months). At final follow‐up the complete success rate (intraocular pressure ≤ 21 Hg without medication) was 92.6% for VC eyes, 96% for phaco VC eyes, 77% for DS eyes and 94% for phaco DS eyes. Kaplan−Meier survival analysis for complete success showed no significant difference between DS and VC nor between phaco VC and phaco DS (p > 0.05). By 36 months postoperatively, mean IOP was 16.8 mmHg (SD 3) in VC eyes, 16.6 mmHg (SD 3.1) in phaco VC eyes, 16.7 mmHg (SD 5.7) in DS eyes and 15 mmHg (SD 3.2) in phaco DS eyes. Postoperative Nd:YAG laser goniopuncture was necessary in 10 eyes in the DS group. Large or cystic drainage blebs occurred only in the DS eyes.Conclusions:  Viscocanalostomy and DS are effective and safe methods of achieving sustained IOP reduction in glaucomatous eyes and both techniques can be successfully combined with cataract extraction.
Detection of oncogenic human papillomavirus in sporadic retinoblastoma
Authors: Palazzi M. A. , Yunes J. A. , Cardinalli I. A. , Stangenhaus G. P. , Brandalise S. R. , Ferreira S. A. , Sobrinho J. S. P. , Villa L. L. 
Published: July 2003

Abstract.Purpose:  To investigate the presence of human papillomavirus (HPV) DNA in tumour tissue from patients with unilateral retinoblastoma.Methods:  Samples of paraffin‐embedded tumour tissue from 43 children with unilateral retinoblastoma were collected to investigate the presence of HPV DNA using polymerase chain reaction (PCR) and dot blot hybridization.Results:  Oncogenic HPV DNA types 16 and 35 were detected in 12 (27.9%) of 43 tumour specimens. A higher frequency of differentiated tumours (63.3%) was observed among the HPV‐positive tumours.Conclusions:  Future studies are necessary to demonstrate an association between HPV and sporadic retinoblastoma.