bluuebunny/crossref_metadata_2025_split huggingface dataset:
The effect of radial head fracture size on elbow kinematics and stability
Authors: Beingessner Daphne M. , Dunning Cynthia E. , Gordon Karen D. , Johnson James A. , King Graham J. W. 
Published: August 2004

AbstractThis study determined the effect of radial head fracture size and ligament injury on elbow kinematics. Eight cadaveric upper extremities were studied in an in vitro elbow simulator. Testing was performed with ligaments intact, with the medial collateral (MCL) or lateral collateral (LCL) ligament detached, and with both the MCL and LCL detached. Thirty degree wedges were sequentially removed from the anterolateral radial head up to 120°. Valgus angulation and external rotation of the ulna relative to the humerus were determined for passive motion, active motion, and pivot shift testing with the arm in a vertical (dependent) orientation. Maximum varus–valgus laxity was calculated from measurements of varus and valgus angulation with the arm in horizontal gravity‐loaded positions. No effect of increasing radial head fracture size was observed on valgus angulation during passive and active motion in the dependent position. In supination, external rotation increased with increasing fracture size during passive motion with LCL deficiency and both MCL and LCL deficiency. With intact ligaments, maximum varus–valgus laxity increased with increasing radial head fracture size. With ligament disruption, elbows were grossly unstable, and no effect of increasing radial head fracture size occurred. During pivot shift testing, performed with the ligaments intact, subtle instability was noted after resection of one‐third of the radial head. In this in vitro biomechanical study, small subtle effects of radial head fracture size on elbow kinematics and stability were seen in both the ligament intact and ligament deficient elbows. These data suggest that fixation of displaced radial head fractures less than or equal to one‐third of the articular diameter may have some biomechanical advantages; however, clinical correlation is required. © 2004 Orthopaedic Research Society. Published by Elsevier Ltd. All rights reserved.
The effect of an ionic detergent on the natively unfolded β‐dystroglycan ectodomain and on its interaction with α‐dystroglycan
Authors: Bozzi Manuela , Di Stasio Enrico , Cicero Daniel O. , Giardina Bruno , Paci Maurizio , Brancaccio Andrea 
Published: August 2004

AbstractDystroglycan (DG) is an adhesion complex, expressed in a wide variety of tissues, formed by an extracellular and a transmembrane subunit, α‐DG and β‐DG, respectively, interacting noncovalently. Recently, we have shown that the recombinant ectodomain of β‐DG, β‐DG(654–750), behaves as a natively unfolded protein, as it is able to bind the C‐terminal domain of α‐DG, while not displaying a defined structural organization. We monitored the effect of a commonly used denaturing agent, the anionic detergent sodium dodecylsulphate (SDS), on β‐DG(654–750) using a number of biophysical techniques. Very low concentrations of SDS (≤2 mM) affect both tryptophan fluorescence and circular dichroism of β‐DG, and significantly perturb the interaction with the α‐DG subunit as shown by solid‐phase binding assays and fluorescence titrations in solution. This result confirms, as recently proposed for natively unfolded proteins, that β‐DG(654–750) exists in a native state, which is crucial to fulfill its biological function. Two‐dimensional NMR analysis shows that SDS does not induce any evident conformational rearrangement within the ectodomain of β‐DG. Its first 70 amino acids, which show a lower degree of mobility, interact with the detergent, but this does not change the amount of secondary structure, whereas the highly flexible and mobile C‐terminal region of β‐DG(654–750) remains largely unaffected, even at a very high SDS concentration (up to 50 mM). Our data indicate that SDS can be used as a useful tool for investigating natively unfolded proteins, and confirm that the β‐DG ectodomain is an interesting model system.
Hexa‐histidin tag position influences disulfide structure but not binding behavior of in vitro folded N‐terminal domain of rat corticotropin‐releasing factor receptor type 2a
Authors: Klose Jana , Wendt Norbert , Kubald Sybille , Krause Eberhard , Fechner Klaus , Beyermann Michael , Bienert Michael , Rudolph Rainer , Rothemund Sven 
Published: August 2004

AbstractThe oxidative folding, particularly the arrangement of disulfide bonds of recombinant extracellular N‐terminal domains of the corticotropin‐releasing factor receptor type 2a bearing five cysteines (C2 to C6), was investigated. Depending on the position of a His‐tag, two types of disulfide patterns were found. In the case of an N‐terminal His‐tag, the disulfide bonds C2–C3 and C4–C6 were found, leaving C5 free, whereas the C‐terminal position of the His‐tag led to the disulfide pattern C2–C5 and C4–C6, and leaving C3 free. The latter pattern is consistent with the disulfide arrangement of the extracellular N‐terminal domain of the corticotropin‐releasing factor (CRF) receptor type 1, which has six cysteines (C1 to C6) and in which C1 is paired with C3. However, binding data of the two differently disulfide‐bridged domains show no significant differences in binding affinities to selected ligands, indicating the importance of the C‐terminal portion of the N‐terminal receptor domains, particularly the disulfide bond C4–C6 for ligand binding.
SPATIAL MARKETS FOR CONSULTANCY TO SMEs
Authors: BENNETT ROBERT J. , SMITH COLIN 
Published: August 2004

ABSTRACTThis paper demonstrates the existence of both localised and national spatial markets for consultancy in Britain. A large survey sample of 1,208 client‐advisor links whose locations are geo‐coded is investigated using GIS software. It is expected from previous literature that search and selection effects, and the transaction costs of interaction at different distances, will influence the selection of consultants by clients. The paper shows that most client‐advisor relationships are geographically close: 61.3 per cent of links are less than 20 km in distance. But there is also a national market whereby 21.9 per cent of consultants are over 100 km and 7.9 per cent are over 200 km from the client. From these patterns, the maximum reach of market areas for different business centres can be estimated. This varies by type of consultancy assignment and size of business centre. The market area is only 30–40 km for consultancy on marketing and sales, and finance and taxation, which are sourced chiefly from local small business centres. For consultancy on business strategy and organisation, product design and quality and training/HR, regional centres and London play a more important role. The paper demonstrates something of a hierarchical structure of consultancy assignments and their spatial markets that is similar to that in retailing.
Empathy, Interaction and Caring: Teachers' Roles in a Constrained Environment
Authors: Cooper Bridget 
Published: August 2004

This paper describes some of the key findings from a recently completed PhD, which examined the role of empathy in teacher–pupil relationships and its relevance to moral modelling. The project collected data through interviews and classroom observations and used grounded methodology theory for the analysis. The literature considers the latest research in neuroscience and the significance of emotions in moral decision making alongside older psychological research on affect and empathy in learning.Despite an overwhelming desire to support, care for and relate deeply to pupils, teachers were continually constrained by the conditions in which they worked. Time was stolen from them by the nature of the current education system; the fragmented and rigid curriculum; the time poor nature of their working conditions; the bureaucracy of modern education and the large numbers of pupils and low frequency of contact. The moral model available for students becomes degraded and needs remain unmet. Teachers are obliged to show lack of care towards individuals, the reverse of what they believe to be necessary and what their pupils want and need.
Linking Product Development Outcomes to Market Valuation of the Firm: The Case of the U.S. Pharmaceutical Industry*
Authors: Sharma Anurag , Lacey Nelson 
Published: August 2004

The purpose of this research was to examine empirically the effects of new product development outcomes on overall firm performance. To do so, first product development and finance literature were connected to develop three testable hypotheses. Next, an event study was conducted in order to explore whether the changes in the stock market valuation of firms are influenced by the outcomes of efforts to develop new products. The pharmaceutical industry was chosen as the empirical context for the present study's analysis largely because the gate‐keeping role played by the Food and Drug Administration (FDA) provides a specific event date on which to focus the event study methodology. As such, this study's events were dates of public announcements of the FDA decisions to approve or to reject the New Drug Applications submitted by the sponsoring firms.Consistent with the efficient market hypothesis, this study's results show that market valuations are responsive strongly and cleanly to the success or failure of new product development efforts. Hence, one of this study's key results suggests that financial markets may be attuned sharply to product development outcomes in publicly traded firms. This study also finds that financial market losses from product development failures were much larger in magnitude than financial market gains from product development successes—indicating an asymmetry in the response of financial markets to the success and failure of new product development efforts. Hence, another implication of this study's results is that managers should factor in a substantial risk premium when considering substantial new development projects. The present study's results also imply that managers should refrain from hyping new products and perhaps even should restrain the enthusiasm that the financial community may build before the product fully is developed. The effect on firm value is severe when expectations about an anticipated new product are not fulfilled. Managers in effect should take care to build reasonable and realistic expectations about potential new products.
Pneumatic balloon dilatation in achalasia: a prospective comparison of safety and efficacy with different balloon diameters
Authors: Mikaeli J. , Bishehsari F. , Montazeri G. , Yaghoobi M. , Malekzadeh R. 
Published: August 2004

AbstractBackground : Pneumatic dilatation is considered to be the first line therapy for achalasia, but long‐term outcome studies are scarce and limited by their retrospective design. There is also no consensus on the optimal method for performing pneumatic dilation as regard to balloon diameter, amount and the rate inflation pressure.Aim : To address these questions in a large long‐term prospective study.Methods : Over a period of 10 years 262 achalasia patients referred to our centre were enrolled. All patients underwent a pre‐treatment clinical evaluation and were followed every 6 months. The first 62 patients (group A) underwent dilatation with initial use of a 35 mm balloon with inflation pressure of 10 psi in 10 seconds (s). In group B (200 patients) we initially used a 30 mm balloon with inflation pressure of 10 psi in 30 s. Dilatation was repeated with incrementally larger balloons (35 and 40 mm) in case of relapse. We used rigiflex balloon and maintained pressure for 60 s after inflation in both groups.Results : Three perforations occurred in group A whereas no perforation took place in Group B. The cumulative proportional remission rate with single dilatation in groups A and B decreased from 83 and 75% in 6 months to 60 and 57% after 30 months of therapy respectively, the differences did not reach statistical significance. In patients who had undergone further dilatations the probability of remaining in remission at 1 year after the first and the second dilatation was 38 and 88% in group A, 20 and 89% in group B respectively. The probability of remaining in remission for 2 years increased from 20% after the first dilatation to 70% after the second dilatation.Conclusion : Graded pneumatic balloon dilatation with 30 mm diameter and slower rate of balloon inflation is an effective and safe initial method of therapy for achalasia. The duration of remission can be extended by repeated dilatation with larger size balloon.
Identifying response to acid suppressive therapy in functional dyspepsia using a random starting day trial – is gastro‐oesophageal reflux important?
Authors: Madsen L. G. , Wallin L. , Bytzer P. 
Published: August 2004

SummaryBackground : Single subject trials offer an alternative approach to identify and characterize responders to a specific treatment.Aim : To test a new single subject trials design, called random starting day trial, to identify acid‐related symptoms in dyspepsia.Methods : A total of 119 patients with functional dyspepsia entered a 12‐day, double‐blind random starting day trial. All patients started on placebo and switched to omeprazole 80 mg/day at a randomized and blinded day between day 5 and day 9, with active treatment continuing for the rest of the trial. Based on changes of a daily symptom score, response was defined as a sustained ≥50% reduction of symptoms within 3 days of active treatment.Results : Thirteen of 119 patients (11%) were classified as spontaneous responders because of complete symptom relief before switching to omeprazole. Of the remaining 106 patients, 15 (15.6%) were classified as responders. Five of six (83%) responders compared with 28 of 53 (53%) non‐responders had pathological reflux. Multivariate testing identified symptoms suggestive of gastro‐oesophageal reflux predictive of response.Conclusions : The random starting day trial design could identify a subset of dyspeptic patients with a uniform symptomatic response to acid‐suppressive therapy. Response seems to be associated with gastro‐oesophageal reflux. The random starting day trial needs to be further validated to be considered as a reliable instrument in clinical research.
A rapid immunochromatographic assay for Helicobacter pylori in stool before and after treatment
Authors: Gatta L. , Perna F. , Ricci C. , Osborn J. F. , Tampieri A. , Bernabucci V. , Miglioli M. , Vaira D. 
Published: August 2004

SummaryBackground : Current guidelines recommend non‐invasive testing and treatment of young dyspeptic patients without alarm symptoms.Aim : To evaluate the accuracy of a new rapid immunochromatographic stool test to diagnose Helicobacter pylori infection before and after treatment compared with a gold standard.Methods : Prospective, single‐blind study, performed in a tertiary care hospital. A total of 303 consecutive dyspeptic patients underwent endoscopy with multiple biopsies. Infected patients were offered a treatment and invited to come back 4–6 weeks after the end of therapy to repeat the endoscopy. Patients were also asked to provide a stool sample before and after therapy.Results : About 149 patients were H. pylori infected. The sensitivity and specificity before treatment were 91.3 and 93.5%; after treatment 92 and 100%. The likelihood ratios were robust enough to produce significant changes from pretest to post‐test probability both in pre‐treatment (LR+ = 14, LR− = 0.093) and post‐treatment (LR+ = 19.6, LR− = 0.095).Conclusions : The novel immunochromatographic stool test is fast, easy to perform and provides good differentiation between positive and negative results. It might become a rapid near patients test easily performed in the doctor office.
Pathogenicity of Stagonospora nodorum requires malate synthase
Authors: Solomon Peter S. , Lee Robert C. , Wilson T. J. Greer , Oliver Richard P. 
Published: August 2004

SummaryA gene encoding malate synthase, a key enzyme of the glyoxylate cycle, has been cloned and characterized in the necrotrophic wheat pathogen Stagonospora nodorum. Expression studies of Mls1 showed high levels of transcript in ungerminated spores whereas malate synthase enzyme activities were low. Expression studies in planta found that Mls1 transcript levels decreased ≈ 10‐fold upon germination before slowly increasing throughout the remainder of the infection. To characterize Mls1 further, the gene was disrupted in S. nodorum by homologous recombination. In the absence of any supplied carbon source, the mls1 spores were unable to germinate and consequently the mutants were non‐pathogenic. Germination and pathogenicity could be restored by the addition of either glucose or sucrose, implying that S. nodorum is reliant upon the catabolism of lipids for infection. Furthermore, analysis of lipid bodies in the mutant strain indicated that lipid mobilization and, consequently, peroxisomal β‐oxidation of fatty acids is delayed or inhibited by the disruption of the glyoxylate cycle. This study has demonstrated for the first time in a fungal phytopathogen the requirement of malate synthase for pathogenicity, suggesting that gluconeogenesis is both dependent on the glyoxylate cycle and required for infection.
Pseudomonas aeruginosa attachment and biofilm development in dynamic environments
Authors: Ramsey Matthew M. , Whiteley Marvin 
Published: August 2004

SummaryBiofilm formation by Pseudomonas aeruginosa is hypothesized to follow a developmental pattern initiated by attachment to a surface followed by microcolony formation and mature biofilm development. Swimming and twitching motility are important for attachment and biofilm development in P. aeruginosa. However, it is clear that many P. aeruginosa strains lacking swimming motility exist as biofilms in the lungs of cystic fibrosis patients. Consequently, we have developed a dynamic attachment assay to identify motility‐independent attachment‐defective mutants. Using transposon mutagenesis, we identified 14 novel dynamic attachment‐deficient (dad) mutants including four mutants specific to dynamic assay conditions (dad specific). Two of the dad‐specific mutants contain insertions in genes involved in sensing and responding to external stimuli, implying a significant impact of external factors on the biofilm developmental pathway. Observations of initial attachment and long‐term biofilm formation characterized our dad mutants into two distinct classes: biofilm delayed and biofilm impaired. Biofilm‐delayed mutants form wild‐type biofilms but are delayed at least 24 h compared with the wild type, whereas biofilm‐impaired mutants never form wild‐type biofilms in our assays. We propose a dynamic model for attachment and biofilm formation in P. aeruginosa including these two classes.
A novel extracellular phospholipase C of Pseudomonas aeruginosa is required for phospholipid chemotaxis
Authors: Barker Adam P. , Vasil Adriana I. , Filloux Alain , Ball Genevieve , Wilderman Paula J. , Vasil Michael L. 
Published: August 2004

Summary Pseudomonas aeruginosa and other bacterial pathogens express one or more homologous extracellular phospholipases C (PLC) that are secreted through the inner membrane via the twin arginine translocase (TAT) pathway. Analysis of TAT mutants of P. aeruginosa uncovered a previously unidentified extracellular PLC that is secreted via the Sec pathway (PlcB). Whereas all presently known PLCs of P. aeruginosa (PlcH, PlcN and PlcB) hydrolyse phosphatidylcholine (PC), only PlcB is active on phosphatidylethanolamine (PE). plcB candidates were identified based on deductions made from bioinformatics data and extant DNA microarray data. Among these candidates, a gene (PA0026) required for the expression of an extracellular PE‐PLC was identified. The protein encoded by PA0026 has limited, but significant similarity, over a short region (∼60aa of 328), to a class of zinc‐dependent prokaryotic PLCs. A conserved His residue of PlcB (His216) that is required for coordinate binding of zinc in this class of PLCs was mutated. Analysis of this mutant established that the protein encoded by PA0026 is PlcB. Three in‐dependent recently published reports indicate that homoserine lactone‐mediated quorum sensing regulates the expression of PA0026 (i.e. plcB). PlcB, but not PlcH or PlcN, is required for directed twitching motility up a gradient of certain kinds of phospholipids. This response shows specificity for the fatty acid moiety of the phospholipid.
Silencing the ap65 gene reduces adherence to vaginal epithelial cells by Trichomonas vaginalis
Authors: Mundodi V. , Kucknoor A. S. , Klumpp D. J. , Chang T. ‐H. , Alderete J. F. 
Published: August 2004

SummaryHost parasitism by Trichomonas vaginalis is complex and in part mediated by adherence to vaginal epithelial cells (VECs). Four trichomonad surface proteins bind VECs as adhesins, and AP65 is a major adhesin with sequence identity to an enzyme of the hydrogenosome organelle that is involved in energy generation. In order to perform genetic analysis and assess the role of AP65 in T. vaginalis adherence, we silenced expression of ap65 using antisense RNA. The gene for ap65 was inserted into the vector pBS‐neo in sense and antisense orientations to generate plasmids pBS‐neoS (S) and pBS‐neoAS (AS), respectively. Trichomonads were then transfected with S and AS plasmids for selection of stable transfectants using Geneticin, and the presence of plasmid in transfectants was confirmed by polymerase chain reaction of the neo gene. Reverse transcription polymerase chain reaction and Northern blot analysis showed decreased amounts of ap65 transcript in AS transfected parasites. Growth kinetics of the antisense‐transfected and wild type organisms were similar, suggesting that silencing AP65 did not affect overall energy generation for growth. Immunoblot analysis using monoclonal antibody (mAb) to AP65 of AS transfectants showed decreased amounts of AP65 when compared to wild type or S transfectants. Not unexpectedly, this corresponded to decreased amounts of AP65 bound to VECs in a functional ligand assay. Reduction in parasite surface expression of AP65 was related to lower levels of adherence to VECs by AS‐transfectants compared to control organisms. Antisense silencing of ap65 was not alleviated by growth of trichomonads in high iron, which up‐regulates transcription of ap65. Our work reaffirms the role for AP65 as an adhesin, and in addition, we demonstrate antisense RNA gene silencing in T. vaginalis to study the contribution of specific genes in pathogenesis.
A family of Candida cell surface haem‐binding proteins involved in haemin and haemoglobin‐iron utilization
Authors: Weissman Ziva , Kornitzer Daniel 
Published: August 2004

SummaryThe ability to acquire iron from host tissues is a major virulence factor of pathogenic microorganisms. Candida albicans is an important fungal pathogen, responsible for an increasing proportion of systemic infections. C. albicans, like many pathogenic bacteria, is able to utilize haemin and haemoglobin as iron sources. However, the molecular basis of this pathway in pathogenic fungi is unknown. Here, we identify a conserved family of plasma membrane‐anchored proteins as haem‐binding proteins that are involved in haem‐iron utilization. We isolated RBT51 as a gene that is sufficient by itself to confer to S. cerevisiae the ability to utilize haemoglobin iron. RBT51 is highly homologous to RBT5, which was previously identified as a gene negatively regulated by the transcriptional suppressor CaTup1. Rbt5 and Rbt51 are mannosylated proteins that carry the conserved CFEM domain. We find that RBT5 is strongly induced by starvation for iron, and that deletion of RBT5 is by itself sufficient to significantly reduce the ability of C. albicans to utilize haemin and haemoglobin as iron sources. Iron starvation‐inducible, antigenically cross‐reacting haem‐binding proteins are also present in other Candida species that are able to utilize haem‐iron, underscoring the conservation of this iron acquisition pathway among pathogenic fungi.